Abstract：
:Healthy aging depends on removal of damaged cellular material that is in part mediated by autophagy. The nutritional status of cells affects both aging and autophagy through as-yet-elusive metabolic circuitries. Here, we show that nucleocytosolic acetyl-coenzyme A (AcCoA) production is a metabolic repressor of autophagy during aging in yeast. Blocking the mitochondrial route to AcCoA by deletion of the CoA-transferase ACH1 caused cytosolic accumulation of the AcCoA precursor acetate. This led to hyperactivation of nucleocytosolic AcCoA-synthetase Acs2p, triggering histone acetylation, repression of autophagy genes, and an age-dependent defect in autophagic flux, culminating in a reduced lifespan. Inhibition of nutrient signaling failed to restore, while simultaneous knockdown of ACS2 reinstated, autophagy and survival of ach1 mutant. Brain-specific knockdown of Drosophila AcCoA synthetase was sufficient to enhance autophagic protein clearance and prolong lifespan. Since AcCoA integrates various nutrition pathways, our findings may explain diet-dependent lifespan and autophagy regulation.
journal_name
Cell Metabjournal_title
Cell metabolismauthors
Eisenberg T,Schroeder S,Andryushkova A,Pendl T,Küttner V,Bhukel A,Mariño G,Pietrocola F,Harger A,Zimmermann A,Moustafa T,Sprenger A,Jany E,Büttner S,Carmona-Gutierrez D,Ruckenstuhl C,Ring J,Reichelt W,Schimmel K,Leedoi
10.1016/j.cmet.2014.02.010subject
Has Abstractpub_date
2014-03-04 00:00:00pages
431-44issue
3eissn
1550-4131issn
1932-7420pii
S1550-4131(14)00066-7journal_volume
19pub_type
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