Cardiolipin stabilizes respiratory chain supercomplexes.
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.
Pfeiffer
Kathy
K
Zentrum der Biologischen Chemie, Universitätsklinikum Frankfurt, D-60590 Frankfurt, Germany.
Gohil
Vishal
V
Stuart
Rosemary A
RA
Hunte
Carola
C
Brandt
Ulrich
U
Greenberg
Miriam L
ML
Schägger
Hermann
H
D025181:ATP Synthetase Complexes / Q000737:chemistry; D001665:Binding Sites; D015153:Blotting, Western; D002308:Cardiolipins / Q000737:chemistry* / Q000378:metabolism; D002384:Catalysis; D002462:Cell Membrane / Q000378:metabolism; D045303:Cytochromes b / Q000737:chemistry; D003575:Cytochromes c1 / Q000737:chemistry; D004072:Digitonin / Q000494:pharmacology; D019281:Dimerization; D004305:Dose-Response Relationship, Drug; D003576:Electron Transport Complex IV / Q000737:chemistry* / Q000378:metabolism; D004591:Electrophoresis, Polyacrylamide Gel; D007202:Indicators and Reagents / Q000494:pharmacology; D007700:Kinetics; D008928:Mitochondria / Q000378:metabolism; D008958:Models, Molecular; D009154:Mutation; D010743:Phospholipids / Q000737:chemistry / Q000378:metabolism; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D012441:Saccharomyces cerevisiae / Q000201:enzymology; D013997:Time Factors
D002308:Cardiolipins; D007202:Indicators and Reagents; D010743:Phospholipids; D045303:Cytochromes b; D003575:Cytochromes c1; D003576:Electron Transport Complex IV; D025181:ATP Synthetase Complexes; D004072:Digitonin