Increased Respiration in the sch9Δ Mutant Is Required for Increasing Chronological Life Span but Not Replicative Life Span

Abstract

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.

TOR and ageing: a complex pathway for a complex process

“…High extracellular acetic acid levels and low pH together formed a toxic combination that accelerated yeast mortality in the post-mitotic environment and appeared to be largely responsible for many measured differences in yeast chronological lifespan, as reversing these effects reversed the lifespan differences. Relevant to this study, both tor1D and sch9D are reported to result in enhanced respiratory activity, possibly limiting acetic acid production by shunting fermentative products into respiratory metabolism [50,98]. Furthermore, the sch9D was found to be resistant to toxicity associated with high levels of acetic acid in a manner requiring RIM15 [110].…”

Reduced Histone Expression or a Defect in Chromatin Assembly Induces Respiration

“…Mitochondrial biogenesis and activity are controlled by the PKA, TOR, Sch9p, Snf1p, and Mec1p/Rad53p signaling pathways (11,(16)(17)(18)(19) and require several transcription factors, including Hap1p, Hap2/3/4/5p, Rtg1/ 3p, and Hcm1p (19)(20)(21)(22)76). Our results show that mitochondrial biogenesis and activity are also regulated by chromatin-mediated pathways.…”

“…The abundance and activity of mitochondria increase, and mitochondria enlarge during the diauxic shift (14,15). Mitochondrial biogenesis and activity are controlled by the protein kinase A (PKA), TOR, Sch9p, Snf1p, and Mec1p/Rad53p signaling pathways (11,(16)(17)(18)(19). The transition from fermentation to oxidative metabolism and the upregulation of mitochondrial biogenesis and activity require several transcription factors, including Hap2/3/4/5p, Cat8p, Rtg1/3p, and Hcm1p (19)(20)(21)(22)(23).…”

Mitochondrial Genomic Dysfunction Causes Dephosphorylation of Sch9 in the Yeast Saccharomyces cerevisiae

“…Sch9 antagonizes Msn2/4 function and promotes the expression of genes encoding ribosomal proteins (23). Moreover, transcription of the genes encoding proteins important for mitochondrial function and mitochondrial ribosomal proteins is induced in sch9⌬ cells (14). Taken together, the behaviors of the genes observed in microarray analysis in 0 cells (21) could be attributed to the decreased Sch9 phosphorylation in 0 cells (Fig.…”