Increased respiration in the sch9 mutant is required for increasing chronological life span but not replicative life span

Biotechnology Research Institute, National Research Council, Montreal, Quebec, H4P 2R2, Canada; Department of Biology, McGill University, Montreal, Quebec, H3A 1B1, Canada

^* To whom correspondence should be addressed. Email: malcolm.whiteway{at}cnrc-nrc.gc.ca.

	Abstract

Loss of the protein kinase Sch9p increases both the chronological and replicative life span (CLS and RLS) of Saccharomyces cerevisiae by mimicking calorie restriction (CR) but the physiological consequences of SCH9 deletion are poorly understood. By transcriptional profiling of an sch9 mutant, we show that mitochondrial electron transport chain genes are up-regulated. Accordingly, protein levels of electron transport chain subunits are increased and the oxygen consumption rate is enhanced in the sch9 mutant. Deletion of HAP4 and CYT1, both essential for respiration, revert the sch9 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 sch9 mutation but had a minor impact on its RLS. SCH9 thus negatively regulates 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 repiratory activity in glucose grown cells.