Increased Respiration in the sch9Δ 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) ofSaccharomyces cerevisiae by mimicking calorie restriction, but the physiological consequences ofSCH9 deletion are poorly understood. By transcriptional profiling of ansch9Δ 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 thesch9Δ mutant. Deletion ofHAP4 andCYT1 , both of which are essential for respiration, revert thesch9Δ mutant respiratory rate back to a lower-than-wild-type level. These alterations of the electron transport chain almost completely blocked CLS extension by thesch9Δ 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 thatTOR1 deletion also increases respiration and that Sch9p is a direct target of TOR signaling, we propose thatSCH9 is one of the major effectors of TOR repression of respiratory activity in glucose grown cells.