Cardiolipin stabilizes respiratory chain supercomplexes

J Biol Chem. 2003 Dec 26;278(52):52873-80. doi: 10.1074/jbc.M308366200. Epub 2003 Oct 15.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • ATP Synthetase Complexes / chemistry
  • Binding Sites
  • Blotting, Western
  • Cardiolipins / chemistry*
  • Cardiolipins / metabolism
  • Catalysis
  • Cell Membrane / metabolism
  • Cytochromes b / chemistry
  • Cytochromes c1 / chemistry
  • Digitonin / pharmacology
  • Dimerization
  • Dose-Response Relationship, Drug
  • Electron Transport Complex IV / chemistry*
  • Electron Transport Complex IV / metabolism
  • Electrophoresis, Polyacrylamide Gel
  • Indicators and Reagents / pharmacology
  • Kinetics
  • Mitochondria / metabolism
  • Models, Molecular
  • Mutation
  • Phospholipids / chemistry
  • Phospholipids / metabolism
  • Protein Conformation
  • Protein Structure, Tertiary
  • Saccharomyces cerevisiae / enzymology
  • Time Factors


  • Cardiolipins
  • Indicators and Reagents
  • Phospholipids
  • Cytochromes b
  • Cytochromes c1
  • Electron Transport Complex IV
  • ATP Synthetase Complexes
  • Digitonin