Crucial Mitochondrial Impairment upon CDC48 Mutation in Apoptotic Yeast

摘要: Mutation in CDC48 (cdc48(S565G)), a gene essential the endo-plasmic reticulum (ER)-associated protein degradation (ERAD) pathway, led to discovery of apoptosis as mechanism cell death unicellular organism Saccharomyces cerevisiae. Elucidating Cdc48p-mediated yeast is particular interest, because Cdc48p highly conserved orthologue human valosin-containing (VCP), pathological effector for polyglutamine disorders and myopathies. Here we show distinct proteomic alterations mitochondria cdc48(S565G) strain. These observed molecular can be related functional impairment these organelles suggested by respiratory deficiency cells. Mitochondrial dysfunction strain accompanied structural damage indicated accumulation cytochrome c cytosol mitochondrial enlargement. We demonstrate reactive oxygen species produced predominantly bc1 complex chain use inhibitors this complex. Concomitantly, emergence caspase-like enzymatic activity occurs suggesting role caspases process. data strongly point first time involvement Cdc48p/VCP-dependent apoptosis.