Respiratory mutations lead to different pleiotropic effects on OXPHOS complexes in yeast and in human cells.
Pleiotropic effects in the oxidative phosphorylation pathway (OXPHOS) were investigated in yeast respiratory mutants and in cells from patients with OXPHOS genetic alterations. The main differences between yeast and human cells were (1) the site of the primary defect that was associated with pleiotropic effects, yeast complex V and human complex IV, and (2) the nature of the complex targeted by the secondary effect, yeast complex IV and human complex I. The pleiotropic effects did not correlate with the organization of OXPHOS into supercomplexes and their functional consequences appeared to be a slowing down of the respiratory chain in order to avoid either an increase in the membrane potential or the accumulation of reduced intermediary components of the respiratory chain.
Marsy
Sophie
S
CNRS, Centre de Génétique Moléculaire, Avenue de la Terrasse, 91198 Gif-sur-Yvette cedex, France.
Frachon
Paule
P
Dujardin
Geneviève
G
Lombès
Anne
A
Lemaire
Claire
C
D000328:Adult; D019069:Cell Respiration / Q000235:genetics; D002478:Cells, Cultured; D002648:Child; D045222:Electron Transport Chain Complex Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D009154:Mutation; D010085:Oxidative Phosphorylation; D012441:Saccharomyces cerevisiae / Q000201:enzymology* / Q000235:genetics
D045222:Electron Transport Chain Complex Proteins