MUTATIONS IN THE MEMBRANE ANCHOR OF YEAST CYTOCHROME C1 COMPENSATE FOR THE ABSENCE OF OXA1P AND GENERATE CARBONATE-EXTRACTABLE FORMS OF CYTOCHROME C1

Oxalp is a mitochondrial inner membrane protein that is mainly require d for the insertion/assembly of complex IV and ATP synthase and is fun ctionally conserved in yeasts, humans, and plants. We have isolated se veral independent suppressors that compensate for the absence of Oxalp . Molecular cloning and sequencing reveal that the suppressor mutation s (CYT1-1 to -6) correspond to amino acid substitutions that are all l ocated in the membrane anchor of cytochrome cl and decrease the hydrop hobicity of this anchor. Cytochrome cl is a catalytic subunit of compl ex III, but the CYT1-1 mutation does not seem to affect the electron t ransfer activity. The double-mutant cyt1-1, 164, which has a drastical ly reduced electron transfer activity, still retains the suppressor ac tivity. Altogether, these results suggest that the suppressor function of cytochrome cl is independent of its electron transfer activity. In addition to the membrane-bound cytochrome cl, carbonate-extractable f orms accumulate in all the suppressor strains. We propose that these c arbonate-extractable forms of cytochrome cl are responsible for the su ppressor function by preventing the degradation of the respiratory com plex subunits that occur in the absence of Oxalp.