E. coli hypoxia-inducible factor ArcA mediates lifespan extension in a lipoic acid synthase mutant by suppressing acetyl-CoA synthetase.
We have previously shown that both the hypoxia-inducible transcription factor ArcA and the PoxB/Acs bypass of the pyruvate dehydrogenase complex contribute to extended lifespan in Escherichia coli. In agreement with studies in higher eukaryotes, we also demonstrated that long-lived E. coli mutants, including LipA-deficient cells, are stress resistant. Here, we show that ArcA contributes to the enhanced lifespan and heat shock resistance of the lipA mutant by suppressing expression of the acetyl-CoA synthetase (acs) gene. The deletion of acs reversed the reduced lifespan of the lipA arcA mutant and promoted the accumulation of extracellular acetate, indicating that inhibition of carbon source uptake contributes to survival extension. However, Acs also sensitized cells lacking ArcA to heat shock, in the absence of extracellular acetate. These results provide evidence for the role of Acs in regulating lifespan and/or stress resistance by both carbon source uptake-dependent and -independent mechanisms.
Gonidakis
Stavros
S
Integrative and Evolutionary Biology, Department of Biological Sciences, University of Southern California, Los Angeles, CA 90089, USA.
Finkel
Steven E
SE
Longo
Valter D
VD
D000106:Acetate-CoA Ligase / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D001425:Bacterial Outer Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D004926:Escherichia coli / Q000201:enzymology / Q000235:genetics* / Q000378:metabolism / Q000502:physiology*; D029968:Escherichia coli Proteins / Q000235:genetics / Q000378:metabolism*; D015964:Gene Expression Regulation, Bacterial / Q000235:genetics; D018869:Heat-Shock Response / Q000235:genetics; D008136:Longevity / Q000235:genetics; D009154:Mutation; D010100:Oxygen / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D013466:Sulfurtransferases / Q000235:genetics*
D001425:Bacterial Outer Membrane Proteins; D029968:Escherichia coli Proteins; D012097:Repressor Proteins; C041610:arcA protein, E coli; D000255:Adenosine Triphosphate; D013466:Sulfurtransferases; C116435:lipoic acid synthase; D000106:Acetate-CoA Ligase; D010100:Oxygen