Cardiolipin Stabilizes Respiratory Chain Supercomplexes*

By K. Pfeiffer, Vishal M. Gohil, R. Stuart, C. Hunte, U. Brandt, M. Greenberg, H. Schägger. Journal of Biological Chemistry, 2003

830 citations recorded by the source corpus.

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.

Subfields: Molecular Biology

View Paper: https://www.semanticscholar.org/paper/8f3636a2df7515a87931e954b42178657da2559b

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In Molecular Biology

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Citations in the corpus

• Reperfusion injury and reactive oxygen species: The evolution of a concept (2015, background): “critical for normal activity of the ETC complexes [313,314].”
• How lipids affect the activities of integral membrane proteins. (2004, background): “Similarly, cardiolipindeficient strains of Saccharomyces cerevisiae are viable under fermenting and non-fermenting conditions, except at high temperatures, showing that cardiolipin is not essential for oxidative phosphorylation [159].”
• Lipids of mitochondria. (2013, background): “Depletion of CL causes dissociation of respiratory chain supercomplexes by releasing cytochrome c oxidase (complex IV) [388].”
• Role of cardiolipin alterations in mitochondrial dysfunction and disease. (2007, background): “CL also plays an essential role in mitochondrial biogenesis (160), and the assembly of respiratory enzyme supercomplexes (138, 192).”
• Biomarkers of mitochondrial content in skeletal muscle of healthy young human subjects (2012, background): “However, it has been suggested to affect inner membrane proton leak (Hoch, 1998) and stabilizing the complexes in the electron transport chain (Pfeiffer et al. 2003).”
• Mitochondrial function as a therapeutic target in heart failure (2016, neutral): “Given that most mitochondrial complexes associated with energy production are oligomers composed of many subunits, cardio-lipin is proposed to act as molecular ‘glue’ holding these subunits together 154–156 .”
• Cytochrome c acts as a cardiolipin oxygenase required for release of proapoptotic factors (2005, background): “, most CL is not free but rather interacts with essentially all mitochondrial electron-transporting complexe”