Correction: PGAM5 promotes lasting FoxO activation after developmental mitochondrial stress and extends lifespan in Drosophila

The Unfolded Protein Responses in Health, Aging, and Neurodegeneration: Recent Advances and Future Considerations

“…For invertebrates as well as mammals, the translational and epigenetic changes induced by the mitochondrial stress signaled through the ATF5-UPR mt result in (1) an upregulation of the expression of mitochondrial chaperones, proteases, protein importers, and ETC components; (2) a reduction in global protein translation in the cytosol; (3) a decrease in protein translation within mitochondria; and (4) a reprogramming of mitochondrial metabolism (Zhao, 2002;Yoneda et al, 2004;Aldridge et al, 2007;Baker et al, 2012;Nargund et al, 2012Nargund et al, , 2015Houtkooper et al, 2013;Gitschlag et al, 2016;Münch and Harper, 2016;Borch Jensen et al, 2018;Molenaars et al, 2020;Yuan et al, 2020). Cumulatively, these effects reduce proteotoxic stress in the mitochondrial matrix by increasing protein folding and degradation capacity, reducing protein burden within the mitochondria, and shifting metabolic demand away from the mitochondria, presumably to allow for the restoration of proper ETC function.…”

“…Across multiple studies investigating the role of UPR mt activation on longevity, a noteworthy trend has emerged: activation of the UPR mt during development appears to confer longevity benefits while initiation of the UPR mt during adulthood does not. Induction of the UPR mt during larval development is sufficient to extend lifespan and maintain the induction of the UPR mt into adulthood (Dillin et al, 2002;Rea et al, 2007;Lee et al, 2010b;Durieux et al, 2011;Borch Jensen et al, 2018;Bazopoulou et al, 2019). It appears that mitochondrial stress during development causes epigenetic changes that induce persistent UPR mt -associated gene changes into adulthood (Merkwirth et al, 2016;Tian et al, 2016;Zhu et al, 2020).…”