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Please use this identifier to cite or link to this item: https://hdl.handle.net/2445/172232
Mitochondrial Complex I Activity Is Required for Maximal Autophagy
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Cells 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.
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THOMAS, Hala Elnakat, et al. Mitochondrial Complex I Activity Is Required for Maximal Autophagy. Cell Reports. 2018. Vol. 24, num. 9, pags. 2404–2417. [consulted: 14 of August of 2026]. Available at: https://hdl.handle.net/2445/172232