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


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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    • "In the mitochondrial inner membrane, CL is involved in stabilising membrane proteins including respiratory complexes [79] and the adenine nucleotide transferase [80]. Furthermore, studies show that CL directly influences the function of the adenine nucleotide transferase [81], an important mitochondrial enzyme that allows the import of ADP into mitochondria for ATP synthesis, and ejects synthesized ATP for use in intracellular processes. "
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    ABSTRACT: Mitochondria play vital roles in metabolic energy transduction, intermediate molecule metabolism, metal ion homeostasis, programmed cell death and regulation of the production of reactive oxygen species. As a result of their broad range of functions, mitochondria have been strongly implicated in aging and longevity. Numerous studies show that aging and decreased lifespan are also associated with high reactive oxygen species production by mitochondria, increased mitochondrial DNA and protein damage, and with changes in the fatty acid composition of mitochondrial membranes. It is possible that the extent of fatty acid unsaturation of the mitochondrial membrane determines susceptibility to lipid oxidative damage and downstream protein and genome toxicity, thereby acting as a determinant of aging and lifespan. Reviewing the vast number of comparative studies on mitochondrial membrane composition, metabolism and lifespan reveals some evidence that lipid unsaturation ratios may correlate with lifespan. However, we caution against simply relating these two traits. They may be correlative but have no functional relation. We discuss an important methodology for body mass and phylogenetic correction in comparative studies.
    03/2014; 3(1):3. DOI:10.1186/2046-2395-3-3
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    • "The activity and stability of the oxidative phosphorylation proteins are affected by their interaction with phospholipids in the IMM. For example, the lack of cardiolipin in IMM was found to destabilize the complexes III and IV of the oxidative phosphorylation system [18, 19], illustrating the importance of CL for mitochondrial respiration. In addition, CL is also involved in the import and assembly of proteins. "
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    ABSTRACT: Mitochondrial membrane phospholipids are essential for the mitochondrial architecture, the activity of respiratory proteins, and the transport of proteins into the mitochondria. The accumulation of phospholipids within mitochondria depends on a coordinate synthesis, degradation, and trafficking of phospholipids between the endoplasmic reticulum (ER) and mitochondria as well as intramitochondrial lipid trafficking. Several studies highlight the contribution of dietary fatty acids to the remodeling of phospholipids and mitochondrial membrane homeostasis. Understanding the role of phospholipids in the mitochondrial membrane and their metabolism will shed light on the molecular mechanisms involved in the regulation of mitochondrial function and in the mitochondrial-related diseases.
    International Journal of Cell Biology 01/2014; 2014(6):709828. DOI:10.1155/2014/709828
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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 · 9.34 Impact Factor
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