Open AccessTor‐Sch9 deficiency activates catabolism of the ketone body‐like acetic acid to promote trehalose accumulation and longevity
Author(s) -
Hu Jia,
Wei Min,
Mirzaei Hamed,
Madia Federica,
Mirisola Mario,
Amparo Camille,
Chagoury Shawna,
Kennedy Brian,
Longo Valter D.
Publication year - 2014
Publication title -
aging cell
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.103
H-Index - 140
eISSN - 1474-9726
pISSN - 1474-9718
DOI - 10.1111/acel.12202
Subject(s) - ketone bodies , biology , catabolism , acetic acid , biochemistry , yeast , trehalose , metabolism , leucine , longevity , amino acid , genetics
Summary In mammals, extended periods of fasting leads to the accumulation of blood ketone bodies including acetoacetate. Here we show that similar to the conversion of leucine to acetoacetate in fasting mammals, starvation conditions induced ketone body‐like acetic acid generation from leucine in S. cerevisiae . Whereas wild‐type and ras2Δ cells accumulated acetic acid, long‐lived tor1Δ and sch9Δ mutants rapidly depleted it through a mitochondrial acetate CoA transferase‐dependent mechanism, which was essential for lifespan extension. The sch9 Δ‐dependent utilization of acetic acid also required coenzyme Q biosynthetic genes and promoted the accumulation of intracellular trehalose. These results indicate that Tor‐Sch9 deficiency extends longevity by switching cells to an alternative metabolic mode, in which acetic acid can be utilized for the storage of stress resistance carbon sources. These effects are reminiscent of those described for ketone bodies in fasting mammals and raise the possibility that the lifespan extension caused by Tor‐S6K inhibition may also involve analogous metabolic changes in higher eukaryotes.