Pfeiffer K, Gohil V, Stuart RA, et al. Cardiolipin stabilizes respiratory chain supercomplexes

Marquette University, Milwaukee, Wisconsin, United States
Journal of Biological Chemistry (Impact Factor: 4.57). 01/2004; 278(52):52873-80. DOI: 10.1074/jbc.M308366200
Source: PubMed

ABSTRACT Cardiolipin stabilized supercomplexes of Saccharomyces cerevisiae respiratory chain complexes III and IV (ubiquinol:cytochrome c oxidoreductase and cytochrome c oxidase, respectively), but was not essential for their formation in the inner mitochondrial membrane because they were found
also in a cardiolipin-deficient strain. Reconstitution with cardiolipin largely restored wild-type stability. The putative
interface of complexes III and IV comprises transmembrane helices of cytochromes b and c1 and tightly bound cardiolipin. Subunits Rip1p, Qcr6p, Qcr9p, Qcr10p, Cox8p, Cox12p, and Cox13p and cytochrome c were not essential for the assembly of supercomplexes; and in the absence of Qcr6p, the formation of supercomplexes was even
promoted. An additional marked effect of cardiolipin concerns cytochrome c oxidase. We show that a cardiolipin-deficient strain harbored almost inactive resting cytochrome c oxidase in the membrane. Transition to the fully active pulsed state occurred on a minute time scale.

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    • "CLs have been shown to interact with different complexes of the inner membrane in mammals and yeast ( McAuley et al . , 1999 ; Zhong et al . , 2004 ; Sharpley et al . , 2006 ) and to stabilize re - spiratory chain supercomplexes ( Pfeiffer et al . , 2003 ; Gebert et al . , 2009 ) . We compared the accumulation of respiratory CI and CI / CIII in Col - 0 and the cls1 mutant by blue native elec - trophoresis ( Figure 6 ) . In dodecyl maltoside – solubilized proteins of Col - 0 and cls1 leaf membrane extracts ( Figure 6A ) , both in - gel NADH / nitroblue tetrazolium ( NBT ) staining , whic"
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    ABSTRACT: Cardiolipin (CL) is the signature phospholipid of the mitochondrial inner membrane. In animals and yeast (Saccharomyces cerevisiae), CL depletion affects the stability of respiratory supercomplexes and is thus crucial to the energy metabolism of obligate aerobes. In eukaryotes, the last step of CL synthesis is catalyzed by CARDIOLIPIN SYNTHASE (CLS), encoded by a single-copy gene. Here, we characterize a cls mutant in Arabidopsis thaliana, which is devoid of CL. In contrast to yeast cls, where development is little affected, Arabidopsis cls seedlings are slow developing under short-day conditions in vitro and die if they are transferred to long-day (LD) conditions. However, when transferred to soil under LD conditions under low light, cls plants can reach the flowering stage, but they are not fertile. The cls mitochondria display abnormal ultrastructure and reduced content of respiratory complex I/complex III supercomplexes. The marked accumulation of tricarboxylic acid cycle derivatives and amino acids demonstrates mitochondrial dysfunction. Mitochondrial and chloroplastic antioxidant transcripts are overexpressed in cls leaves, and cls protoplasts are more sensitive to programmed cell death effectors, UV light, and heat shock. Our results show that CLS is crucial for correct mitochondrial function and development in Arabidopsis under both optimal and stress conditions.
    The Plant Cell 10/2013; 25(10). DOI:10.1105/tpc.113.118018 · 9.58 Impact Factor
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    • "Respiratory chain complexes are associated into supercomplexes in yeast, mammalian (Schägger and Pfeiffer, 2000) and plant mitochondria (Van Lis et al., 2003; Eubel et al., 2004; Dudkina et al., 2006a). In yeast, cardiolipins stabilize these supercomplexes (Pfeiffer et al., 2003). It has also been established that interactions between ATP synthase monomers leads to the formation of dimers and oligomers. "
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    ABSTRACT: Mitochondrial F(1)F(o) ATP synthase is an enzymatic complex involved in the aerobic synthesis of ATP. It is well known that several enzymes are organized in supramolecular complexes in the inner mitochondrial membrane. The ATP synthase supramolecular assembly is mediated through two interfaces. One leads to dimer formation and the other to oligomer formation. In yeast, the presence of ATP synthase oligomers has been described as essential to the maintenance of the mitochondrial cristae ultrastructure. Indeed, the destabilization of the interactions between monomers was shown to alter the organization of the inner mitochondrial membrane, leading to the formation of onion-like structures similar to those observed in some mitochondrial pathologies. By using information obtained this decade (structure modeling, electron microscopy and cross-linking), this paper (i) reviews the actual state of the art and (ii) proposes a topological model of the transmembrane domains and interfaces of the ATP synthase's tetramer. This review also discusses the physiological role of this oligomerization process and its potential implications in mammal pathology. This article is part of a Directed Issue entitled: Bioenergetic Dysfunction, adaptation and therapy.
    The international journal of biochemistry & cell biology 06/2012; 45(1). DOI:10.1016/j.biocel.2012.05.017 · 4.24 Impact Factor
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    • "Lipocalin-2 modifies the composition of C18:2 acyl chains in the phospholipids sub-fractions PC and PI, as well as the mitochondrial inner membrane phospholipids , cardiolipin, a phospholipid critically involved in regulating mitochondrial structure, oxidative phosphorylation and biogenesis [35] [36]. Cardiolipin binding is essential for the stability of respiratory chain supercomplexes and oxidative generation of ATP [37]. Structurally, cardiolipin consists of two phosphatidyl residues linked by a glycerol moiety and attached with a total of four fatty acyl chains [38]. "
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    ABSTRACT: Recent clinical and experimental evidences demonstrate an association between augmented circulating lipocalin-2 [a pro-inflammatory adipokine] and cardiac dysfunction. However, little is known about the pathophysi-ological role of lipocalin-2 in heart. The present study was designed to compare the heart functions of mice with normal (WT) or deficient lipocalin-2 (Lcn2-KO) expression. Echocardiographic analysis revealed that the myocardial contractile function was significantly improved in hearts of Lcn2-KO mice, under both standard chow and high fat diet conditions. The heart function before and after I/R injury (20-min of global ischemia followed by 60-min of reperfusion) was assessed using the Langendorff perfusion system. Compared to WT littermates, hearts from Lcn2-KO mice showed improved functional recovery and reduced infarct size following I/R. Under baseline condition, the mitochondrial function of Lcn2-KO hearts was significantly enhanced, as demonstrated by biochemical analysis of respiratory chain activity and markers of biogenesis, as well as electron microscopic investigation of the mitochondrial ultrastructure. Acute or chronic administration of lipocalin-2 impaired cardiac functional recovery to I/R and dampened the mitochondrial function in hearts of Lcn2-KO mice. These effects were associated with an extensive modification of the fatty acyl chain compositions of intracellular phospholipids. For example, lipocalin-2 facilitated the redistribution of linoleic acid (C18:2) among different types of phospholipids, including cardiolipin, a structurally unique phospholipid located mainly on the inner membrane of mitochondria. Lack of lipocalin-2 improved the functional recovery of isolated mice hearts subjected to I/R, which is associated with restoration of mitochondrial function and phospholipids remodeling.
    American Journal of Translational Research 01/2012; 4(1):60-71. · 3.23 Impact Factor
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