TY - JOUR
T1 - In Salmonella enterica, the sirtuin-dependent protein acylation/deacylation system (SDPADS) maintains energy homeostasis during growth on low concentrations of acetate
AU - Chan, Chi Ho
AU - Garrity, Jane
AU - Crosby, Heidi A.
AU - Escalante-Semerena, Jorge C.
PY - 2011/4
Y1 - 2011/4
N2 - Acetyl-coenzyme A synthetase (Acs) activates acetate into acetyl-coenzyme A (Ac-CoA) in most cells. In Salmonella enterica, acs expression and Acs activity are controlled. It is unclear why the sirtuin-dependent protein acylation/deacylation system (SDPADS) controls the activity of Acs. Here we show that, during growth on 10mM acetate, acs+ induction in a S. enterica strain that cannot acetylate (i.e. inactivate) Acs leads to growth arrest, a condition that correlates with a drop in energy charge (0.17) in the acetylation-deficient strain, relative to the energy charge in the acetylation-proficient strain (0.71). Growth arrest was caused by elevated Acs activity, a conclusion supported by the isolation of a single-amino-acid variant (AcsG266S), whose overproduction did not arrest growth. Acs-dependent depletion of ATP, coupled with the rise in AMP levels, prevented the synthesis of ADP needed to replenish the pool of ATP. Consistent with this idea, overproduction of ADP-forming Ac-CoA-synthesizing systems did not affect the growth behaviour of acetylation-deficient or acetylation-proficient strains. The AcsG266S variant was >2 orders of magnitude less efficient than the AcsWT enzyme, but still supported growth on 10mM acetate. This work provides the first evidence that SDPADS function helps cells maintain energy homeostasis during growth on acetate.
AB - Acetyl-coenzyme A synthetase (Acs) activates acetate into acetyl-coenzyme A (Ac-CoA) in most cells. In Salmonella enterica, acs expression and Acs activity are controlled. It is unclear why the sirtuin-dependent protein acylation/deacylation system (SDPADS) controls the activity of Acs. Here we show that, during growth on 10mM acetate, acs+ induction in a S. enterica strain that cannot acetylate (i.e. inactivate) Acs leads to growth arrest, a condition that correlates with a drop in energy charge (0.17) in the acetylation-deficient strain, relative to the energy charge in the acetylation-proficient strain (0.71). Growth arrest was caused by elevated Acs activity, a conclusion supported by the isolation of a single-amino-acid variant (AcsG266S), whose overproduction did not arrest growth. Acs-dependent depletion of ATP, coupled with the rise in AMP levels, prevented the synthesis of ADP needed to replenish the pool of ATP. Consistent with this idea, overproduction of ADP-forming Ac-CoA-synthesizing systems did not affect the growth behaviour of acetylation-deficient or acetylation-proficient strains. The AcsG266S variant was >2 orders of magnitude less efficient than the AcsWT enzyme, but still supported growth on 10mM acetate. This work provides the first evidence that SDPADS function helps cells maintain energy homeostasis during growth on acetate.
UR - http://www.scopus.com/inward/record.url?scp=79953058855&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=79953058855&partnerID=8YFLogxK
U2 - 10.1111/j.1365-2958.2011.07566.x
DO - 10.1111/j.1365-2958.2011.07566.x
M3 - Article
C2 - 21306440
AN - SCOPUS:79953058855
SN - 0950-382X
VL - 80
SP - 168
EP - 183
JO - Molecular Microbiology
JF - Molecular Microbiology
IS - 1
ER -