Increased respiration in the sch9Delta mutant is required for increasing chronological life span but not replicative life span.
Loss of the protein kinase Sch9p increases both the chronological life span (CLS) and the replicative life span (RLS) of Saccharomyces cerevisiae by mimicking calorie restriction, but the physiological consequences of SCH9 deletion are poorly understood. By transcriptional profiling of an sch9Delta mutant, we show that mitochondrial electron transport chain genes are upregulated. Accordingly, protein levels of electron transport chain subunits are increased and the oxygen consumption rate is enhanced in the sch9Delta mutant. Deletion of HAP4 and CYT1, both of which are essential for respiration, revert the sch9Delta mutant respiratory rate back to a lower-than-wild-type level. These alterations of the electron transport chain almost completely blocked CLS extension by the sch9Delta mutation but had a minor impact on the RLS. SCH9 thus negatively regulates the CLS and RLS through inhibition of respiratory genes, but a large part of its action on life span seems to be respiration independent and might involve increased resistance to stress. Considering that TOR1 deletion also increases respiration and that Sch9p is a direct target of TOR signaling, we propose that SCH9 is one of the major effectors of TOR repression of respiratory activity in glucose grown cells.
Lavoie
Hugo
H
Biotechnology Research Institute, National Research Council, Montreal, Quebec H4P 2R2, Canada.
Whiteway
Malcolm
M
D023081:CCAAT-Binding Factor / Q000235:genetics / Q000378:metabolism; D045222:Electron Transport Chain Complex Proteins / Q000235:genetics / Q000378:metabolism; D015966:Gene Expression Regulation, Fungal; D046228:Microarray Analysis; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism; D010641:Phenotype; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000201:enzymology* / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D017384:Sequence Deletion
D023081:CCAAT-Binding Factor; D045222:Electron Transport Chain Complex Proteins; C061437:HAP4 protein, S cerevisiae; D024101:Mitochondrial Proteins; D029701:Saccharomyces cerevisiae Proteins; D017346:Protein Serine-Threonine Kinases; C530964:SCH9 protein, S cerevisiae