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molecules
Review
The Role of Taurine in Mitochondria Health: More Than Just
an Antioxidant
Chian Ju Jong 1, *, Priyanka Sandal 1and Stephen W. Schaffer 2
Citation: Jong, C.J.; Sandal, P.;
Schaffer, S.W. The Role of Taurine in
Mitochondria Health: More Than Just
an Antioxidant. Molecules 2021,26,
4913. https://doi.org/10.3390/
molecules26164913
Academic Editors: Elena Grasselli,
Chiara Lambruschini, Lisa Moni and
Ilaria Demori
Received: 29 July 2021
Accepted: 10 August 2021
Published: 13 August 2021
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1
Neuroscience and Pharmacology, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA;
priyanka-sandal@uiowa.edu
2Department of Pharmacology, College of Medicine, University of South Alabama, Mobile, AL 36688, USA;
sschaffe@southalabama.edu
*Correspondence: chianju-jong@uiowa.edu
Abstract:
Taurine is a naturally occurring sulfur-containing amino acid that is found abundantly in
excitatory tissues, such as the heart, brain, retina and skeletal muscles. Taurine was first isolated
in the 1800s, but not much was known about this molecule until the 1990s. In 1985, taurine was
first approved as the treatment among heart failure patients in Japan. Accumulating studies have
shown that taurine supplementation also protects against pathologies associated with mitochondrial
defects, such as aging, mitochondrial diseases, metabolic syndrome, cancer, cardiovascular diseases
and neurological disorders. In this review, we will provide a general overview on the mitochondria
biology and the consequence of mitochondrial defects in pathologies. Then, we will discuss the
antioxidant action of taurine, particularly in relation to the maintenance of mitochondria function. We
will also describe several reported studies on the current use of taurine supplementation in several
mitochondria-associated pathologies in humans.
Keywords: taurine; mitochondria; antioxidant; 5-taurinomethyluridine; oxidative stress; apoptosis
1. Introduction
Mitochondrial dysfunction, along with oxidative stress, is a key hallmark of various
pathologies, such as aging [
1
,
2
], cardiovascular diseases [
3
,
4
], mitochondrial diseases [
5
,
6
],
metabolic syndrome [
7
,
8
], cancer [
9
,
10
] and neurological disorders, such as neurodegen-
erative diseases [
11
,
12
] and neurodevelopmental disorders [
13
,
14
]. Often, antioxidant
therapy, such as coenzyme Q [
15
], mitoQ [
16
,
17
], vitamin E [
18
], gingko biloba extracts [
19
],
ebselen [
20
], creatine [
21
], lipoic acid [
22
], melatonin [
23
,
24
] and L-arginine [
25
,
26
], pro-
vide some protections, potentially by improving the mitochondrial function and reducing
oxidative stress in these diseases. Recently, taurine, a sulfur-containing amino acid, has
been approved in Japan in treating stroke-like episodes in patients with mitochondrial
myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS), which is a
mitochondrial disease [
27
,
28
]. Indeed, the use of taurine dates back to 1985, as taurine
was first used to treat patients with congestive heart failure in Japan [
29
,
30
]. In addition,
taurine supplementation has been shown to improve the exercise capacity of patients with
heart failure [
31
], which is likely due to improvement of the myocardial energy production.
Although taurine was first identified in the 1800s [
32
], the mitochondrial actions of taurine
still remain unclear and underappreciated. This review, therefore, will provide an overview
of the significant role of taurine in the maintenance of mitochondrial function. Clinical
studies using taurine therapy in mitochondria-targeted pathologies will also be discussed.
2. Mitochondria Biology
Mitochondria are cellular organelles that regulate various essential cellular pro-
cesses [
33
–
37
]. The mitochondria consist of two membranes, an ion impermeable inner
membrane and a permeable outer membrane, which envelopes a soluble matrix containing
Molecules 2021,26, 4913. https://doi.org/10.3390/molecules26164913 https://www.mdpi.com/journal/molecules
Molecules 2021,26, 4913 2 of 21
cristae [
38
]. There are hundreds of mitochondria in one cell and each mitochondrion con-
tains 2–10 copies of mitochondrial DNA (mtDNA) [39]. The mtDNA encodes 13 polypep-
tides, which are components of the electron transport chain, as well as two ribosomal
RNAs (rRNA) and 22 transfer RNAs (tRNA), which regulate the synthesis of mitochondrial
proteins [
40
]. Predominantly known as the powerhouse of the cell, mitochondria provide
cellular energy by generating ATP via oxidative phosphorylation. Reducing equivalents,
such as NADH and FADH
2
, produced via the tricarboxylic acid (TCA) cycle, deliver elec-
trons along the electron transport chain to reduce molecular oxygen to water. The influx of
electrons along the electron transport chain creates a transmembrane proton gradient that
drives ATP synthesis via the ATP synthase (F
o
F
1
complex synthase) [
41
]. A consequence of
electron transport along the electron transport chain is the generation of reactive oxygen
species (ROS), where one electron reduces molecular oxygen to produce a superoxide
anion (O
2
−·
) [
42
]. When catalyzed by the antioxidant superoxide dismutase (SOD), O
2
−·
is dismutated to hydrogen peroxide (H
2
O
2
) and molecular oxygen. H
2
O
2
can be further
partially reduced to a hydroxyl radical (OH−), which is a highly reactive species [42].
The mitochondria are the main source of superoxide production, primarily via Com-
plex I and Complex III of the electron transport chain [
43
,
44
]. Under normal conditions, 2%
of electrons are diverted to reduce molecular oxygen to produce a superoxide [
42
]. Physio-
logically, ROS has been shown to regulate various crucial cellular processes, such as cellular
differentiation [
45
,
46
], autophagy [
47
,
48
], metabolic adaptation [
49
,
50
] and immune cell
activation [
50
–
52
]. Pathologically, ROS has often been shown to cause harm to cells, which
are described as follow. One, ROS is capable of inducing mitochondrial and nuclear DNA
damage [
53
,
54
]. Two, ROS causes irreversible protein oxidation. ROS oxidizes the side
chain of four key amino acids, lysine, arginine, proline and threonine, which adds ketone
or aldehyde groups to proteins and alters the protein structure and function [
55
,
56
]. Three,
ROS oxidizes cellular and organelle membranes, which consist of polyunsaturated fatty
acids [
57
]. Cardiolipin is a unique phospholipid localized in the inner membrane of the
mitochondria as it contains a polar head group that traps protons for oxidative phosphory-
lation [
58
], three glycerol backbones and four acyl chains [
59
]. A phospholipid generally
consists of a polar headgroup, a glycerol backbone and hydrophobic acyl chains [
60
]. There
has been increasing evidence showing cardiolipin being crucial for the functionality of the
mitochondria. Primarily, cardiolipin maintains the structural integrity of the mitochondrial
membranes [
61
,
62
], as well as stability and proper functioning of proteins and enzyme
complexes involved in oxidative phosphorylation [
63
–
65
]. Oxidation of cardiolipin induces
mitochondrial dysfunction, as has been shown in several
in vitro
studies. These studies
have shown impaired cellular metabolism and a sluggish activity of the electron transport
chain [
64
,
66
,
67
], as well as enhanced cell death, as evidenced by mitochondrial permeability
transport pore opening and cytochrome c release [
68
,
69
]. To counteract excessive ROS
production, the cell contains an antioxidant defense system, which encompasses enzymatic
antioxidants such as mitochondria-localized manganese superoxide dismutase (MnSOD),
cytosolic-localized zinc SOD (ZnSOD) and copper SOD (CuSOD), catalase and glutathione
peroxidase. MnSOD, ZnSOD and CuSOD catalyze the dismutation of O
2
−
into water and
H
2
O
2
[
42
]. Both catalase and glutathione peroxidase break down H
2
O
2
into water and
oxygen [
42
,
70
]. When ROS is excessively produced, it can overwhelm the antioxidant
defenses and this causes oxidative stress [
71
,
72
]. Often, increased oxidative stress further
exacerbates cellular damage [73,74].
3. Mitochondria in Pathologies
Impairment of mitochondrial function has been commonly reported in pathologies
such as aging, cardiovascular diseases, mitochondrial diseases, metabolic syndrome, cancer
and neurological disorders [
1
–
7
,
9
–
11
,
13
,
14
,
75
]. Often, these pathologies are character-
ized by increased ROS production [
1
,
2
], reduced ATP generation [
5
,
7
],
apoptosis [75,76]
,
impaired mitochondrial biogenesis [
4
,
76
], impaired activity of electron transport
chain [3,7,77]
and mitochondrial calcium mishandling [
4
]. Recently, increasing evidence
Molecules 2021,26, 4913 3 of 21
from
in vitro
[
78
–
84
] and
in vivo
[
85
–
89
] studies has demonstrated the beneficial effects of
taurine in maintaining mitochondrial functions.
4. Taurine Biology
Taurine or 2-aminoethane-sulfonic acid is a unique amino acid as it has a sulfonyl
group on the C-terminus and an amino group residing on the
β
-carbon (Figure 1a) rather
than
α
-carbon (Figure 1b) [
90
]. Taurine, therefore, is a
β
-sulfonic amino acid
(Figure 1)
.
Taurine was first identified by Tiedemann and Gmelin, who isolated taurine in 1827 from
the bile of the ox, Bos taurus [
32
]. As described in Figure 2, taurine (
5
) is synthesized
in the liver from methionine (
1
) or cysteine (
2
) to produce hypotaurine (
4
) by cysteine
dioxygenase and cysteine sulfonic acid decarboxylase (CSAD). Cysteine dioxygenase
converts methionine or cysteine (
1
–
2
) to cysteinesulfinate (
3
), while CSAD converts cysteine
sulfinate (
3
) to hypotaurine (
4
). Hypotaurine (
4
) is then readily oxidized to taurine (5),
which may be excreted directly or as a conjugate with bile salts such as taurocholate (
6
) [
90
].
Molecules 2021, 26, x FOR PEER REVIEW 3 of 22
3. Mitochondria in Pathologies
Impairment of mitochondrial function has been commonly reported in pathologies
such as aging, cardiovascular diseases, mitochondrial diseases, metabolic syndrome, can-
cer and neurological disorders [1–7,9–11,13,14,75]. Often, these pathologies are character-
ized by increased ROS production [1,2], reduced ATP generation [5,7], apoptosis [75,76],
impaired mitochondrial biogenesis [4,76], impaired activity of electron transport chain
[3,7,77] and mitochondrial calcium mishandling [4]. Recently, increasing evidence from in
vitro [78–84] and in vivo [85–89] studies has demonstrated the beneficial effects of taurine
in maintaining mitochondrial functions.
4. Taurine Biology
Taurine or 2-aminoethane-sulfonic acid is a unique amino acid as it has a sulfonyl
group on the C-terminus and an amino group residing on the β-carbon (Figure 1a) rather
than α-carbon (Figure 1b) [90]. Taurine, therefore, is a β-sulfonic amino acid (Figure 1).
Taurine was first identified by Tiedemann and Gmelin, who isolated taurine in 1827 from
the bile of the ox, Bos taurus [32]. As described in Figure 2, taurine (5) is synthesized in the
liver from methionine (1) or cysteine (2) to produce hypotaurine (4) by cysteine dioxygen-
ase and cysteine sulfonic acid decarboxylase (CSAD). Cysteine dioxygenase converts me-
thionine or cysteine (1–2) to cysteinesulfinate (3), while CSAD converts cysteine sulfinate
(3) to hypotaurine (4). Hypotaurine (4) is then readily oxidized to taurine (5), which may
be excreted directly or as a conjugate with bile salts such as taurocholate (6) [90].
(a)
(b)
Figure 1. (a) Taurine or 2-aminoethane-sulfonic acid is a β-sulfonic amino acid as it has a sulfonyl
group rather than a carboxyl group attached to the alpha carbon and an amino group on the beta
carbon; (b) a standard amino acid contains an alpha carbon, to which an both an amino group and
a carboxyl group are attached.
Figure 1.
(
a
) Taurine or 2-aminoethane-sulfonic acid is a
β
-sulfonic amino acid as it has a sulfonyl
group rather than a carboxyl group attached to the alpha carbon and an amino group on the beta
carbon; (
b
) a standard amino acid contains an alpha carbon, to which an both an amino group and a
carboxyl group are attached.
Molecules 2021, 26, x FOR PEER REVIEW 4 of 22
Figure 2. Taurine (5) is synthesized from either methionine (1) or cysteine (2). Cysteine dioxygenase catalyzes the conver-
sion of cysteine (2) to cysteinesulfinate (3), which then is converted to hypotaurine (4) by cysteine sulfinate decarboxylase.
Hypotaurine (4) is readily oxidized to form taurine (5), which can be excreted directly or as a conjugate with bile acids
such as taurocholate (6).
In most mammals including humans, rodents and some primates, taurine is consid-
ered a conditionally essential amino acid, as cysteine dioxygenase and CSAD are present
abundantly. Mammals primarily depend on taurine biosynthesis in vivo [91] and partially
from diet, such as from meat, seafood and human milk [92–94]. Newborns and young
infants are unable to synthesize taurine as well as adult humans, and therefore, are de-
pendent on a taurine-supplemented diet [95]. Clinical studies investigating infants sup-
plemented with (30–40 μM/dL) or without taurine showed that inadequate taurine sup-
plementation impairs lipid absorption and bile acid secretion and causes hepatic and ret-
inal dysfunction [96–99]. Due to the importance of taurine in neonatal development, moth-
ers are strongly encouraged to breastfeed, due to the high concentration of taurine in
breast milk, or feed infants with taurine-supplemented formulas and taurine-supple-
mented total parenteral nutrition [97,99,100]. On the other hand, the activities of taurine
biosynthetic enzymes are low in cats, dogs and foxes, and therefore they primarily depend
on a taurine-supplemented diet [101,102]. When fed with a diet deficient in taurine, these
animals developed pathologies such as cardiomyopathy and myocardial dysfunction
[101,103,104], retinal and tapetal degeneration that leads to blindness [105–107], neurolog-
ical abnormalities [108,109], weakened immune response [110], pregnancy and fetal de-
velopment complications [111,112], as well as gastrointestinal problems [113,114]. In con-
trast, when fed with taurine-supplemented diets, these animals were protected against
pathologies such as cardiomyopathy [115,116], seizure [108,117], and retinopathy [118],
and showed improved reproductive performance and neurological development [119].
Taurine has also been added to energy drinks such as Red Bull, Monster, Tab Energy and
Rockstar [120]. It was estimated that on average, there is 750 mg of taurine in an 8 oz can
of energy drink [120]. While energy drinks mainly provide an energy boost, the exact role
of taurine in energy drinks remains unclear as energy drinks also contain additional ad-
ditives such as caffeine, ginseng, vitamins, antioxidants and sugars [121]. However, two
reviews by Kurtz et al. [122] and Seidel et al. [123] have described the influence of taurine
on exercise performance.
Figure 2.
Taurine (
5
) is synthesized from either methionine (
1
) or cysteine (
2
). Cysteine dioxygenase catalyzes the conversion
of cysteine (
2
) to cysteinesulfinate (
3
), which then is converted to hypotaurine (
4
) by cysteine sulfinate decarboxylase.
Hypotaurine (
4
) is readily oxidized to form taurine (
5
), which can be excreted directly or as a conjugate with bile acids such
as taurocholate (6).
Molecules 2021,26, 4913 4 of 21
In most mammals including humans, rodents and some primates, taurine is consid-
ered a conditionally essential amino acid, as cysteine dioxygenase and CSAD are present
abundantly. Mammals primarily depend on taurine biosynthesis
in vivo
[
91
] and par-
tially from diet, such as from meat, seafood and human milk [
92
–
94
]. Newborns and
young infants are unable to synthesize taurine as well as adult humans, and therefore,
are dependent on a taurine-supplemented diet [
95
]. Clinical studies investigating infants
supplemented with (30–40
µ
M/dL) or without taurine showed that inadequate taurine sup-
plementation impairs lipid absorption and bile acid secretion and causes hepatic and retinal
dysfunction [
96
–
99
]. Due to the importance of taurine in neonatal development, mothers
are strongly encouraged to breastfeed, due to the high concentration of taurine in breast
milk, or feed infants with taurine-supplemented formulas and taurine-supplemented total
parenteral nutrition [
97
,
99
,
100
]. On the other hand, the activities of taurine biosynthetic
enzymes are low in cats, dogs and foxes, and therefore they primarily depend on a taurine-
supplemented diet [
101
,
102
]. When fed with a diet deficient in taurine, these animals
developed pathologies such as cardiomyopathy and myocardial dysfunction [
101
,
103
,
104
],
retinal and tapetal degeneration that leads to blindness [
105
–
107
], neurological abnor-
malities [
108
,
109
], weakened immune response [
110
], pregnancy and fetal development
complications [
111
,
112
], as well as gastrointestinal problems [
113
,
114
]. In contrast, when
fed with taurine-supplemented diets, these animals were protected against pathologies
such as cardiomyopathy [
115
,
116
], seizure [
108
,
117
], and retinopathy [
118
], and showed
improved reproductive performance and neurological development [
119
]. Taurine has also
been added to energy drinks such as Red Bull, Monster, Tab Energy and Rockstar [
120
].
It was estimated that on average, there is 750 mg of taurine in an 8 oz can of energy
drink [
120
]. While energy drinks mainly provide an energy boost, the exact role of taurine
in energy drinks remains unclear as energy drinks also contain additional additives such
as caffeine, ginseng, vitamins, antioxidants and sugars [
121
]. However, two reviews by
Kurtz et al. [
122
] and Seidel et al. [
123
] have described the influence of taurine on exercise
performance.
Taurine is ubiquitously expressed in most tissues, particularly in the excitable tissues
such as the heart, retina, brain and muscles [
32
]. The intracellular concentration of taurine
is commonly 5–50 mM and the plasma concentration of taurine is approximately 100
µ
M.
When taurine is supplemented, the plasma taurine content usually reaches its peak within
1 h to 2.5 h of taurine intake [
124
,
125
]. Ghandforoush-Sattari et al. [
124
] conducted an
analysis on the pharmacokinetics of oral taurine supplementation (4 g) in healthy adults.
These individuals, who had fasted overnight, showed a baseline taurine content in a
range of 30
µ
mol to 60
µ
mol. Then, 1.5 h after taurine intake, the plasma taurine content
increased to approximately 500
µ
mol. Plasma taurine content subsequently decreased to
baseline level 6.5 h after taurine intake. This study would be consistent with the common
notion that excess plasma taurine is mostly excreted via urine or being transported to
tissues. As taurine is only synthesized in the liver, maintenance of a high concentration
of taurine in other tissues depends on the taurine uptake from the blood via a sodium-
dependent taurine transporter (TauT). This TauT has a higher affinity for
β
-amino acids,
such as taurine, but a lower affinity for
α
-amino acids [
90
]. The importance of this taurine
transporter has been evidenced in mouse models lacking the TauT gene [
126
,
127
], as well
as in
in vivo
and
in vitro
studies utilizing taurine transporter competitive inhibitors, such
as β-alanine [128,129] or guanidinoethanesulfonate (GES) [130,131].
Two mouse models lacking the TauT (TauTKO) were generated by Ito’s group [
126
] and
Warskulat’s group [
127
]. Both TauTKO mouse models had reduced taurine concentrations
in the heart, skeletal muscles and retina, validating the requirement of the taurine transport
from the liver to these tissues [
126
,
127
]. As a consequence of taurine deficiency, these
TauTKO mice developed retinal degeneration, chronic liver disease, muscle atrophy, a
decrease in exercise capacity and increased susceptibility to streptozotocin-induced diabetic
nephropathy [
126
,
127
,
132
–
134
]. The TauTKO mice developed by the Ito’s group also
showed evidence of cardiomyopathy, as indicated by diminished fractional shortening;
Molecules 2021,26, 4913 5 of 21
ventricular remodeling, as shown by dilated ventricles; and reductions in ventricular
wall thickness, as well as increased expression of fetal genes that serve as heart failure
markers, such as atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP) and
β
-myosin heavy chain (MHC) [
126
]. Further examination of the TauTKO hearts revealed
mitochondrial swelling and disruption of the outer mitochondrial membrane, as well
as a reduction in the activity of succinate dehydrogenase (SDH), which is a marker of
mitochondrial enzyme [
126
]. In addition, TauTKO hearts contained defective mitochondria,
as evidenced by smaller mitochondria size, impaired activities of the electron transport
chain, oxidative stress and apoptosis [
135
]. The TauTKO hearts were also associated with
impaired autophagy, which is the cellular quality control in degrading damaged proteins
or organelles [
136
,
137
]. Defective mitochondria and impaired autophagy in TauTKO hearts,
therefore, may contribute to the underlying development of cardiomyopathy in TauTKO
mice. In addition, the same TauTKO mice showed premature aging, as characterized by
shortened lifespan and acceleration of skeletal muscle senescence [
138
]. Interestingly, while
the TauTKO mice developed by the Warskulat’s group showed normal cardiac function,
the expression of fetal genes such as ANP, BNP and CARP (cardiac ankyrin repeat protein)
increased in the TauTKO hearts, suggesting taurine depletion may predispose the mice to
the development of a heart failure [
127
]. Based on the studies from these mouse models
that lacked the TauT, it is convincing that taurine indeed has multiple physiological roles
that include maintaining mitochondrial function.
Similarly, pharmacological inhibition of taurine transport using
β
-alanine or GES
in both
in vitro
and
in vivo
studies resulted in significant pathological conditions, which
include atrophic cardiac remodeling [
126
,
139
,
140
], oxidative stress [
141
,
142
], increased
apoptosis [
143
], mitochondrial defects [
83
,
84
] and altered cardiac cell morphology [
144
],
as well as loss of retinal ganglion cells that lead to retinopathy [
128
]. All these studies
clearly demonstrated the importance of taurine as a cytoprotective agent with multiple
physiological functions. Recently, increasing studies have focused on the antioxidant role
of taurine in maintaining mitochondrial function.
5. Taurine as a Therapeutic Agent in Mitochondrial Dysfunction
Various
in vitro
and
in vivo
studies have reported that taurine supplementation pro-
tects against mitochondrial dysfunction. Homma et al. [
82
] recently showed that taurine
protects against metabolic impairment and mitochondrial dysfunction in MELAS patient-
derived undifferentiated induced pluripotent stem cells (iPSCs) and the iPSC-derived
retinal pigment epithelium (RPE). In a clinical study on oral taurine supplementation
among MELAS patients, Ohsawa et al. [
27
] reported that taurine reduces the incidence of
stroke-like episodes and increases the taurine modification of mitochondrial tRNA
Leu(UUR)
.
Shetewy et al. [
83
] showed that taurine pretreatment protects against mitochondria dam-
age and mitochondria fission in beta-alanine-treated mouse embryonic fibroblasts. Jong
et al. [
84
] also showed that taurine pretreatment protects against the effect of beta-alanine-
mediated taurine depletion on the opening of the mitochondrial permeability transition
pore and subsequently inhibited apoptosis. In rat cardiomyocytes, taurine supplementa-
tion inhibits glucose-deprivation-induced mitochondrial oxidative stress, mitochondrial
dysfunction, apoptosis and ER stress [
78
]. The aforementioned studies are some examples
describing the protective roles of taurine in maintaining mitochondria health. In the follow-
ing sections, we describe several mechanisms by which taurine may regulate mitochondrial
health. All these mechanisms are summarized in Figure 3.
Molecules 2021,26, 4913 6 of 21
Molecules 2021, 26, x FOR PEER REVIEW 6 of 22
5. Taurine as a Therapeutic Agent in Mitochondrial Dysfunction
Various in vitro and in vivo studies have reported that taurine supplementation pro-
tects against mitochondrial dysfunction. Homma et al. [82] recently showed that taurine
protects against metabolic impairment and mitochondrial dysfunction in MELAS patient-
derived undifferentiated induced pluripotent stem cells (iPSCs) and the iPSC-derived ret-
inal pigment epithelium (RPE). In a clinical study on oral taurine supplementation among
MELAS patients, Ohsawa et al. [27] reported that taurine reduces the incidence of stroke-
like episodes and increases the taurine modification of mitochondrial tRNALeu(UUR). Shet-
ewy et al. [83] showed that taurine pretreatment protects against mitochondria damage
and mitochondria fission in beta-alanine-treated mouse embryonic fibroblasts. Jong et al.
[84] also showed that taurine pretreatment protects against the effect of beta-alanine-me-
diated taurine depletion on the opening of the mitochondrial permeability transition pore
and subsequently inhibited apoptosis. In rat cardiomyocytes, taurine supplementation in-
hibits glucose-deprivation-induced mitochondrial oxidative stress, mitochondrial dys-
function, apoptosis and ER stress [78]. The aforementioned studies are some examples
describing the protective roles of taurine in maintaining mitochondria health. In the fol-
lowing sections, we describe several mechanisms by which taurine may regulate mito-
chondrial health. All these mechanisms are summarized in Figure 3.
Figure 3. Taurine is known not as a radical scavenger. Several potential mechanisms by which tau-
rine exerts its antioxidant activity in maintaining mitochondria health include: taurine conjugates
with uridine on mitochondrial tRNA to form a 5-taurinomethyluridine for proper synthesis of mi-
tochondrial proteins (mechanism 1), which regulates the stability and functionality of respiratory
chain complexes; taurine reduces superoxide generation by enhancing the activity of intracellular
antioxidants (mechanism 2); taurine prevents calcium overload and prevents reduction in energy
production and the collapse of mitochondrial membrane potential (mechanism 3); taurine directly
scavenges HOCl to form N-chlorotaurine in inhibiting a pro-inflammatory response (mechanism 4);
and taurine inhibits mitochondria-mediated apoptosis by preventing caspase activation or by re-
storing the Bax/Bcl-2 ratio and preventing Bax translocation to the mitochondria to promote apop-
tosis (mechanism 5).
5.1. Taurine Forms a Complex with Mitochondrial tRNA
Taurine is primarily a free amino acid, although it does conjugate with bile acids to
form taurocholate [90]. In 2002, a group of Japanese scientists discovered that taurine is a
Figure 3.
Taurine is known not as a radical scavenger. Several potential mechanisms by which
taurine exerts its antioxidant activity in maintaining mitochondria health include: taurine conjugates
with uridine on mitochondrial tRNA to form a 5-taurinomethyluridine for proper synthesis of
mitochondrial proteins (mechanism 1), which regulates the stability and functionality of respiratory
chain complexes; taurine reduces superoxide generation by enhancing the activity of intracellular
antioxidants (mechanism 2); taurine prevents calcium overload and prevents reduction in energy
production and the collapse of mitochondrial membrane potential (mechanism 3); taurine directly
scavenges HOCl to form N-chlorotaurine in inhibiting a pro-inflammatory response (mechanism
4); and taurine inhibits mitochondria-mediated apoptosis by preventing caspase activation or by
restoring the Bax/Bcl-2 ratio and preventing Bax translocation to the mitochondria to promote
apoptosis (mechanism 5).
5.1. Taurine Forms a Complex with Mitochondrial tRNA
Taurine is primarily a free amino acid, although it does conjugate with bile acids to
form taurocholate [
90
]. In 2002, a group of Japanese scientists discovered that taurine is
a component of the mitochondrial tRNAs [
145
]. Specifically, they identified two taurine-
containing modified uridines, namely 5-taurinomethyluridine (
τ
m
5
u) and 5-taurinomethyl-
2-thiouridine (
τ
m
5
s
2
u). These conjugates are linked to the role of taurine as an antioxi-
dant. Taurine conjugates with uridine at the anticodon wobble position of mitochondrial
tRNA
Leu(UUR)
or mitochondrial tRNA
Lys
to form
τ
m
5
u and
τ
m
5
s
2
u, respectively [
145
,
146
].
These conjugation reactions, which are catalyzed by the mitochondrial optimization 1
(Mto1) in mammals [
147
], are required for precise anticodon–codon interactions for proper
synthesis of mitochondrial-encoded proteins [148].
Based on the wobble hypothesis, the nucleoside at the first position of the anticodon
forms hydrogen bonds with the third nucleoside of the codon, forming a wobble base pair.
Normally, uridine at the anticodon wobble position base pairs with either adenine (A) or
guanine (G) at the codon position of mRNA, which translates for leucine codons (UUA
and UUG). An unmodified uridine at the anticodon wobble position can base pair with
all four bases, A, G, cytosine (C) and uracil (U) at the third position of the codon [
146
].
These pairings subsequently result in mistranslation, as it also translates for phenylalanine
codons (UUC and UUU) in addition to the usual leucine codons. However, when taurine
conjugates with uridine at the anticodon wobble position, the taurine-modified uridine base
pairs only with either adenine or guanine of the corresponding codons and translates for
Molecules 2021,26, 4913 7 of 21
leucine codons (UUA and UUG) [
145
,
148
,
149
]. This proper anticodon–codon interaction is
significantly important for proper expression of mitochondrial-encoded proteins [
149
,
150
],
implicating the significance of post-transcriptional modification of uridine through taurine
conjugation at the anticodon wobble position of mitochondrial tRNA
Leu(UUR)
. The impor-
tance of post-transcriptional modifications in tRNAs lies not only in ensuring proper codon
recognition for translation accuracy, they are also essential in improving the efficiency
of tRNA and facilitating the codon recognition by elongation factors or aminoacyl-tRNA
synthetases. Consequently, a mutation in the post-transcriptional modification of mito-
chondrial tRNA
Leu(UUR)
can affect protein synthesis as it can decrease RNase P processing,
tRNA stability and aminoacylation, resulting in an abnormal tRNA conformation [150].
A defect in taurine conjugation of mitochondrial tRNA
Leu(UUR)
, which prevents the
formation of 5-taurinomethyl-uridine, has been implicated in mitochondrial myopathy,
encephalopathy, lactic acidosis and stroke-like episodes (MELAS), as well as myoclonus
epilepsy associated with ragged-red fibers (MERRF) [
82
,
145
,
146
,
148
,
149
]. Indeed, an early
study by Kirino et al. [
149
] showed that unmodified uridine of mitochondrial tRNA
Leu(UUR)
weakens the binding affinity for the UUG codon, which could result in inefficient synthesis
of mitochondrial proteins. Among the 13 polypeptides that encode mitochondrial proteins,
ND5, ND6 and cytochrome b contain two, eight and two UUG codons, respectively. A
deficiency in taurine conjugation of mitochondrial tRNA
Leu(UUR)
, therefore, may affect the
synthesis of mitochondrial proteins. Indeed, Jong et al. [
129
] have shown a reduction in
the protein levels of ND5 and ND6 in beta-alanine-treated cells. Both ND5 and ND6 are
components of the complex I of the electron transport chain. A reduction in the expres-
sion of mitochondrial proteins ND5 and ND6 then cause the instability of the complex I,
which could cause a sluggish transport of electrons across the respiratory chain, as well as
diversion of electrons to oxygen to form a superoxide. Excessive superoxide production
then can promote oxidative stress and overwhelm the antioxidant defenses [
84
,
129
]. In-
deed, a recent study by Fakruddin et al. [
147
] showed that defective taurine-containing
mitochondrial tRNA modification causes mitochondrial dysfunction and disrupts global
protein homeostasis, thereby suggesting the significance of taurine-containing uridine
modification in regulating global protein homeostasis. When taurine was supplemented,
Homma et al. [
82
] observed an increase in the taurine modification of the mitochondrial
tRNA
Leu(UUR)
, as well as an improvement in the mitochondrial function in the iPSC gen-
erated from a MELAS patient. While many other studies [
28
,
78
,
81
–
84
,
88
,
89
,
93
,
99
,
117
,
145
]
have shown that taurine supplementation protects against mitochondrial dysfunction
without definite underlying mechanisms, it is likely that the antioxidant function of taurine
is associated with its role in the conjugation reaction with the uridine of the mitochondrial
tRNALeu(UUR). However, this matter will require further validation.
5.2. Taurine Reduces Superoxide Generation in the Mitochondria
There have been many studies showing taurine as an antioxidant with a role in pro-
tecting against oxidative stress in the mitochondria [
27
,
28
,
78
,
81
–
84
,
88
,
89
,
93
,
99
,
117
,
136
,
145
].
However, the underlying mechanism by which taurine protects against oxidative stress in
the mitochondria remains unclear, as Aruoma et al. [
151
] showed that taurine is not a radical
scavenger. It is important to note that while taurine is incapable of scavenging classical ROS,
taurine is a direct scavenger of hypochlorous acid (HOCl), which is generated from hydro-
gen peroxide (H
2
O
2
) in the presence of chloride ions, producing N-chlorotaurine [
151
,
152
].
The role of N-chlorotaurine is mainly in regulating the inflammatory response. Specifically,
N-chlorotaurine has been shown to activate nuclear factor (erythroid-derived 2)-like 2
(Nrf2), which is a transcription factor that controls the transcription of various antioxidant
genes and subsequently prevents inflammation [153–155].
While recent studies have suggested that the prevention of superoxide in the mito-
chondria is linked to the taurine conjugation of the mitochondrial tRNA [
28
,
82
,
84
,
147
],
several studies have shown that taurine may exert its antioxidant function via different
mechanisms. In germ cells, taurine has been shown to protect against oxidative stress by
Molecules 2021,26, 4913 8 of 21
promoting the activity of Cu/Zn SOD [
156
]. Cu/Zn SOD is localized in the mitochondrial
intermembrane space activity [
157
,
158
]. Indeed, taurine increases the protein levels but
not mRNA levels of Cu/Zn SOD, suggesting that taurine mediates the effects of Cu/Zn
SOD at the protein level. In another study by Tabassum et al. [
159
], the antioxidant role
of taurine was attributed to the enhancement of intracellular reduced glutathione (GSH).
GSH is essential for detoxification of xenobiotics, where GSH is oxidized to GSSG (oxidized
glutathione) during oxidative stress. In a tamoxifen-treated liver, there is a reduction
in the GSH levels, which increases the susceptibility to oxidative stress due to impaired
antioxidant defense system. When tamoxifen-treated mice were co-treated with taurine,
the GSH level was restored and oxidative stress was prevented. These findings suggest the
physiological role of taurine in stabilizing the intracellular GSH levels. Other earlier studies
by Pasantes et al. [
160
–
162
] have also suggested that taurine protects lipid membranes
from tamoxifen-induced oxidative damage by acting as a membrane stabilizer, rather than
directly acting against the oxidants. Indeed, a review by Hansen et al. [
163
] described the
role of taurine as a buffer in the mitochondria matrix to stabilize the pH gradient across the
inner mitochondrial membranes.
5.3. Taurine Regulates Intracellular Calcium Homeostasis
Several studies from El-Idrissi’s group have shown that taurine regulates intracellu-
lar calcium homeostasis and protects against glutamate-induced mitochondrial damage
and cell death [
164
–
168
]. In general, glutamate increases the intracellular calcium level
and causes the collapse of the mitochondrial membrane potential and induces cell death.
However, when cultured cerebellar granule cells were pretreated with glutamate, taurine
prevented an increase in the mitochondrial calcium level, prevented mitochondrial mem-
brane depolarization and prevented an impairment in the mitochondrial function [
166
].
One of the functions of mitochondria is energy metabolism, which is regulated by cal-
cium. In glutamate-induced excitotoxicity, a collapse in the mitochondrial membrane
potential causes a depletion in the energy production, as measured by ATP levels, and
promotes neuronal death. However, when neuronal cells were pretreated with taurine,
the glutamate-induced excitotoxicity effects were inhibited, along with increased energy
metabolism [
165
]. Meanwhile, additional studies [
169
–
172
] have shown taurine also regu-
lates calcium homeostasis to maintain cardiac contractile function. In general, heart failure
is caused by impaired contraction due to calcium mishandling, which reduces the calcium
sensitivity of the contractile proteins, and insufficient ATP generation to drive contraction.
Studies by Steele et al. [
173
] and Galler et al. [
174
] showed that physiological concentrations
of taurine increase the calcium sensitivity of contractile proteins and modulate cardiac
contractility. As calcium is known to regulate mitochondrial oxidative phosphorylation to
produce ATP [
175
], regulation of intracellular calcium homeostasis by taurine can improve
the energy production through maintenance of mitochondrial function.
5.4. Taurine Inhibits Mitochondria-Mediated Apoptosis
It has been thought that taurine acts at the level of mitochondria to inhibit apopto-
sis. Indeed, Jong et al. [
135
] showed that TauTKO hearts pretreated with mitotempo, a
mitochondria-targeted antioxidant, were protected against oxidative stress and mitochon-
drial apoptosis. Interestingly, Takatani et al. [
79
] showed that taurine pretreatment does not
prevent the release of cytochrome c and the reduction in mitochondria membrane potential
during ischemia. However, taurine pretreatment prevents ischemia-induced cleavage
of caspase 9 and caspase 3 [
79
]. Generally in apoptosis signaling, cytochrome c, Apaf-1
and caspase 9 form a complex known as apoptosome, which activates caspase 9 and the
subsequent downstream caspase-3-mediated signaling cascade [
176
]. In another study by
Leon et al. [
177
], it was shown that taurine protects against glutamate-induced apoptosis
by inhibiting glutamate-induced membrane depolarization, potentially by acting on the
chloride channels and preventing excessive calcium influx. As a result, glutamate-induced
activation of calpain is inhibited, which then prevents Bax translocation to the mitochondria
Molecules 2021,26, 4913 9 of 21
and the subsequent cytochrome c release. Similar mechanisms have also been reported
by Wu and Prentice [
178
,
179
]. Similarly, Taranukhin et al. [
180
] showed that taurine pre-
vents ethanol-induced mitochondria-mediated apoptosis by increasing the levels of Bcl-2.
Restoration of Bax:Bcl-2 levels prevents Bax translocation to the mitochondria, and thus
protects against activation of the mitochondria-mediated apoptosis.
6. Clinical Application of Taurine in Mitochondria-Targeted Pathologies
Several clinical studies investigating the therapeutic potential of taurine have been
reported, particularly in relation to its role as an antioxidant in improving mitochondrial
function. Below, we report several known clinical studies on taurine supplementation in
various pathologies in humans.
6.1. Cardiovascular Diseases
Taurine was first used to treat heart failure patients by Azuma’s group in
Japan [
29
,
30
,
181
]. Most heart failure patients receiving taurine supplementation (2–3 g
taurine daily for a range of four to eight weeks) showed improvement in the systolic left
ventricular function, as evidenced by increased cardiac output and stroke volume, ejection
fraction and mean velocity of circumferential fiber shortening. When comparing the effects
of taurine to coenzyme Q
10
, no significant improvement in the systolic left ventricular
function was observed [
181
]. Coenzyme Q
10
is an antioxidant that mediates the transfer
of electrons from complex I and complex II to complex III [
42
]. In heart failure patients,
the levels of coenzyme Q
10
were reduced and supplementation with coenzyme Q
10
was
shown to improve the symptoms among heart failure patients [
182
–
184
]. The effectiveness
of taurine, but not coenzyme Q
10
, in improving myocardial energy in heart failure suggests
the significant effect of taurine as an antioxidant, potentially by improving the myocardial
energy production. In heart failure, a disturbance in ATP production affects myocardial
contraction [
185
,
186
], thereby suggesting the significance of taurine in improving mito-
chondrial function through restoration of myocardial energy production. Similarly, another
study conducted among heart failure patients in NYHA class II or III receiving 500 mg
of taurine supplementation three times a day for two weeks showed improved exercise
capacity [
31
]. Again, this study implicates the role of taurine as an antioxidant to improve
mitochondrial function, potentially through restoration of energy production.
Taurine has also been supplemented among patients with hypertension. Taurine
supplementation of 1.6 g per day for at least 12 weeks in prehypertensive patients or 6 g
per day for 7 days in hypertensive patients lowered blood pressure and improved vascular
function [
187
,
188
]. In addition, worldwide epidemiological studies among 61 different pop-
ulation groups in 25 different countries have reported that regular taurine intake through
daily consumption of seafood, nuts, soy and milk reduces the prevalence of cardiovascular
diseases that include hypertension and hypercholesterolemia [
94
,
189
–
192
]. While the un-
derlying mechanisms by which taurine attenuates hypertension remain unclear, several
in vitro
and
in vivo
studies have suggested the antioxidant activity of taurine in reducing
hypertension, which include reducing ROS generation [
193
,
194
], improving ATP produc-
tion [
195
] and improving mitochondrial metabolism [
196
]. Indeed, hypertension has been
largely associated with mitochondrial dysfunction, which includes mitochondrial oxidative
stress [197], alteration of mitochondrial homeostasis and impaired energy production.
6.2. Metabolic Syndrome
Taurine supplementation among patients with type II diabetes mellitus also showed
reduced oxidative stress and inflammation, as well as reduced diabetic complications,
such as nephropathy, retinopathy and neuropathy [
198
–
200
]. In diabetic patients, plasma
taurine concentrations have been reported to be reduced when compared to healthy control
patients [201–203]. This reduction is associated with higher renal excretion of taurine and
a lower intestinal absorption of taurine, suggesting a depletion in the bioavailability of
taurine in diabetic patients [
199
,
201
–
203
]. Normal plasma taurine concentration has been
Molecules 2021,26, 4913 10 of 21
reported to be about 44
µ
mol/L, while the normal whole blood taurine concentration is
averaged to be 227
µ
mol/L in fasting humans [
204
]. Indeed, several
in vitro
and
in vivo
studies have also reported reduced taurine concentrations in diabetic models, which often
are associated with impaired glucose tolerance, insulin resistance and impaired glucose
and lipid metabolism [
201
,
202
,
205
–
207
]. It is well known that diabetic complications
arise from hyperglycemia-induced oxidative stress, which usually originates from the
mitochondrial respiratory chain as the primary source [
208
]. As a result of mitochondrial
oxidative stress, the functions of the mitochondria are impaired, which are the main
source of glucose and fatty acid metabolism. When taurine is supplemented, glucose
levels are restored, insulin secretion is enhanced and glucose and lipid metabolism in the
mitochondria are stimulated [
209
–
212
]. As an antioxidant, taurine potentially suppresses
excessive oxidants generation in the mitochondria and maintains the functionality of
mitochondria. While taurine is not known as a radical scavenger [
151
], the underlying
mechanism of taurine as an antioxidant could potentially occur through conjugation with
uridine of mitochondrial tRNA, equilibration of intracellular antioxidants or stabilization
of mitochondrial homeostasis.
Despite the effectiveness of taurine in reducing diabetic complications in several
clinical trials, there are a few studies contradicting the clinical effectiveness of taurine in
diabetic patients. Firstly, Franconi et al. [
202
] reported that oral taurine supplementation of
1.5 g/day for 90 days in patients with insulin-dependent diabetes mellitus did not improve
glucose metabolism, although plasma taurine concentration increased significantly in dia-
betic patients. Secondly, Chauncey et al. [
213
] reported that oral taurine supplementation
of 3 g/day for 4 months among type 2 diabetic patients increased plasma taurine content
but did not reduce the plasma glucose levels. Thirdly, Nakamura et al. [
214
] reported that
oral taurine supplementation of 3 g/day for 12 months in patients with microalbuminuria
of non-insulin-dependent diabetes mellitus increased plasma taurine content but did not
reduce microalbuminuria, which is a strong marker of diabetic nephropathy.
Taurine has also been administered in overweight or obese individuals, which has
shown promising therapeutic effects on lipid profiles. Rosa et al. [
215
] reported that obese
women supplemented with 3 g/day of taurine for eight weeks had a significant increase
in the content of both plasma taurine and adiponectin and a significant decrease in pro-
inflammatory markers and the lipid peroxidation marker. In a separate study by Mizushima
et al. [
216
], healthy individuals were given high-fat and high-cholesterol diets for three
weeks. At the same time, when these individuals were also given 6 g/day of taurine for
three weeks, the increase in the levels of total cholesterol and low density lipoprotein (LDL)-
cholesterol was attenuated. De Carvalho et al. [
217
] recently showed that a combination of
3 g taurine supplementation and exercise training for eight weeks among obese women
improved lipid metabolism and mitochondrial activity in the subcutaneous white adipose
tissue. In addition, regular taurine intake through daily consumption of seafood, nuts,
soy and milk has been shown to reduce the prevalence of metabolic syndrome, which
includes obesity [
94
,
189
–
192
]. This observation is based on worldwide epidemiological
studies conducted in more than 60 different populations around the world [
218
]. The
antioxidant role of taurine in modulating the lipid profiles in obesity is likely to occur
through maintenance of mitochondrial homeostasis and suppression of oxidative stress that
stimulates lipid metabolism and subsequent restoration of energy production [
215
–
217
].
Indeed, this is consistent with several
in vivo
and
in vitro
studies on metabolic syndrome,
showing the suppression of lipid peroxidation and restoration of mitochondrial function
with taurine treatment [219–223].
6.3. Mitochondrial Diseases
Recent studies on mitochondrial diseases such as MELAS and MERRF revealed a
reduction in the formation of taurine-modified uridine of mitochondrial tRNAs, specifically
5-taurinomethyluridine (
τ
m
5
u) and 5-taurinomethyl-2-thiouridine (
τ
m
5
s
2
u) [
145
,
148
,
149
].
When taurine was supplemented, Homma et al. [
82
] observed an increase in the taurine
Molecules 2021,26, 4913 11 of 21
modification of the mitochondrial tRNA
Leu(UUR)
, as well as improvement of the mitochon-
drial function in the iPSC generated from a MELAS patient. Indeed, oral taurine supple-
mentation of either 9 g or 12 g per day for 52 weeks in MELAS patients showed prevention
of stroke-like episodes, as well as increased modification of taurine-conjugated uridine
of mitochondrial tRNA
Leu(UUR)
[
27
,
28
]. In a separate study by Fukuda and Nagao [
224
],
plasma taurine content was reduced in one Japanese man diagnosed with MELAS and ma-
ternally inherited diabetes and deafness (MIDD). While the taurine-containing modification
of mitochondrial tRNA was not examined in this study, it is plausible that the formation of
taurine-modified uridine was absent due to low plasma taurine content. Therefore, it is
likely that oral taurine supplementation in this MELAS/MIDD patient could potentially
increase the plasma taurine content, enhance taurine-containing modification of uridine
and improve his clinical symptoms. Indeed, the significance of the taurine-containing
modification of uridine has been established in several
in vitro
and
in vivo
studies that
demonstrated the efficiency of mitochondrial protein synthesis, improvement of mitochon-
drial respiratory activity, restoration of energy production, suppression of oxidative stress
and maintenance of global protein homeostasis [27,28,82,145,148,149,224].
6.4. Neurological Disorders
Currently, there are no reported clinical studies on taurine supplementation among
patients with neurodegenerative diseases. However, there have been some
in vivo
studies
assessing the therapeutic effects of taurine in several mouse models of neurodegenerative
diseases, which include Parkinson’s disease [
225
,
226
] and Alzheimer’s disease [
227
–
230
].
In these studies, it has been concluded that taurine suppresses pathological changes by
maintaining the mitochondrial homeostasis. A common feature in neurodegenerative
diseases is glutamate-mediated hyperexcitability that leads to calcium overload, collapse in
mitochondrial membrane potential and increased ROS production [
231
–
236
]. As mitochon-
drial damage is commonly observed in neurodegenerative diseases [
233
–
235
], it is sensible
to presume that the cellular damage is caused by the mitochondrial ROS production.
Indeed, several studies investigating the underlying mechanisms of neurodegenerative
diseases have reported a reduction in the respiratory chain activity, a decrease in the ATP
production, a collapse in the mitochondrial membrane potential and an increase in mi-
tochondrial ROS production [
11
,
234
,
235
,
237
,
238
]. As taurine is known to modulate the
mitochondrial function, it is plausible that taurine supplementation would improve the
clinical symptoms in patients with neurodegenerative diseases.
The clinical effectiveness of taurine in neurodevelopmental disorders has been re-
ported in several studies by Erickson et al. [
239
–
243
]. These clinical studies used acam-
prosate, which is a synthetic taurine analogue. Acamprosate is approved by the United
States Food and Drug Administration (FDA) to treat alcohol dependence [
244
]. In the
first study, oral acamprosate supplementation of 1 g/day for 21 weeks in three adults
with Fragile-X syndrome showed significant improvement in communication [
240
]. In the
second study, oral acamprosate supplementation of 1 g/day for 10 weeks in twelve young
children with Fragile-X syndrome and comorbid autism spectrum disorders showed signif-
icant improvement in social skills and inattention/hyperactivity [
243
]. Additional studies
on oral acamprosate supplementation of 1 g/day for 20 weeks in young children with
autism spectrum disorders showed significant improvement in social deficits [
239
,
241
,
242
].
Neurodevelopmental disorders are commonly characterized by excessive glutamater-
gic and deficient GABAergic neurotransmission, which is associated with social impair-
ment [
245
–
247
]. Glutamate excitotoxicity can lead to calcium overload, collapse in mito-
chondrial membrane potential and increased mitochondrial ROS production, which can
cause mitochondrial dysfunction [
231
–
236
]. Many studies have increasingly shown the
link between neurodevelopmental disorders and mitochondrial dysfunction [
248
–
250
]. As
acamprosate is an analogue of taurine, which is an antioxidant that maintains the mito-
chondrial homeostasis, it is plausible that acamprosate improves the clinical symptoms in
neurodevelopmental disorders by maintaining the mitochondrial homeostasis.
Molecules 2021,26, 4913 12 of 21
7. Conclusions
Taurine is a simple but unique sulfur-containing amino acid that has multiple phys-
iological functions, including the maintenance of mitochondria health. While taurine is
widely known as an antioxidant, its underlying mechanism remains unclear as taurine
is not a radical scavenger. Studies conducted by Suzuki and colleagues have shown that
taurine conjugates with mitochondrial tRNA
Leu(UUR)
or tRNA
Lys(UUU)
for proper codon–
anticodon interaction to facilitate synthesis of mitochondrial-encoded proteins. Inefficiency
of taurine modification of mitochondrial tRNA promotes inefficient translation of mito-
chondrial proteins, which are components of the electron transport chain. As a result,
the assembly and stability of the respiratory chain complexes are impaired, which causes
a sluggish response in the electron flux, yielding superoxide production. Taurine also
regulates intracellular calcium homeostasis and intracellular antioxidant activity and in-
hibits apoptosis. As evidenced in many
in vitro
,
in vivo
and clinical studies on taurine
supplementation, the occurrence of mitochondrial dysfunction, reduced energy production,
oxidative stress and apoptosis are mostly inhibited. Taurine therapy, therefore, could po-
tentially improve mitochondrial health, particularly in mitochondria-targeted pathologies,
such as cardiovascular diseases, metabolic diseases, mitochondrial diseases and neurologi-
cal disorders. Whether the protective mechanism on mitochondria primarily relies on the
taurine modification of mitochondrial tRNA requires further investigation.
Author Contributions:
Writing—original draft preparation, C.J.J.; writing—review and editing,
C.J.J. and P.S.; supervision, S.W.S. All authors have read and agreed to the published version of the
manuscript.
Funding: This research received no external funding.
Conflicts of Interest: The authors declare no conflict of interest.
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