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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Available from: Vishal M Gohil, Nov 02, 2015
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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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    • "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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    • "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.
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