Thomas, Hala ElnakatZhang, YuStefely, Jonathan A.Veiga, Sonia Rosa Pereira daThomas, GeorgeKozma, Sara C.Mercer, Carol A.2020-11-202020-11-202018-08-28https://hdl.handle.net/2445/172232Cells adapt to nutrient and energy deprivation by inducing autophagy, which is regulated by the mammalian target of rapamycin (mTOR) and AMP-activated protein kinases (AMPKs). We found that cell metabolism significantly influences the ability to induce autophagy, with mitochondrial complex I function being an important factor in the initiation, amplitude, and duration of the response. We show that phenformin or genetic defects in complex I suppressed autophagy induced by mTOR inhibitors, whereas autophagy was enhanced by strategies that increased mitochondrial metabolism. We report that mTOR inhibitors significantly increased select phospholipids and mitochondrial-associated membranes (MAMs) in a complex I-dependent manner. We attribute the complex I autophagy defect to the inability to increase MAMs, limiting phosphatidylserine decarboxylase (PISD) activity and mitochondrial phosphatidylethanolamine (mtPE), which support autophagy. Our data reveal the dynamic and metabolic regulation of autophagy.application/pdfengcc by nc-nd (c) Thomas et al., 2018http://creativecommons.org/licenses/by-nc-nd/3.0/es/AutofàgiaMitocondrisAutophagyMitochondriainfo:eu-repo/semantics/article2020-11-11info:eu-repo/semantics/openAccess30157433