Department of Molecular, Cell and Cancer Biology; UMass Metabolic Network
Biochemistry | Cell Biology | Cellular and Molecular Physiology | Molecular Biology
In Caenorhabditis elegans, the programmed repression of the heat shock response (HSR) accompanies the transition to reproductive maturity, leaving cells vulnerable to environmental stress and protein aggregation with age. To identify the factors driving this event, we performed an unbiased genetic screen for suppressors of stress resistance and identified the mitochondrial electron transport chain (ETC) as a central regulator of the age-related decline of the HSR and cytosolic proteostasis. Mild downregulation of ETC activity, either by genetic modulation or exposure to mitochondria-targeted xenobiotics, maintained the HSR in adulthood by increasing HSF-1 binding and RNA polymerase II recruitment at HSF-1 target genes. This resulted in a robust restoration of cytoplasmic proteostasis and increased vitality later in life, without detrimental effects on fecundity. We propose that low levels of mitochondrial stress regulate cytoplasmic proteostasis and healthspan during aging by coordinating the long-term activity of HSF-1 with conditions preclusive to optimal fitness.
HSF-1, aging, heat shock response, mitochondria, proteostasis, stress resistance
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© 2017 The Author(s).
DOI of Published Version
Cell Rep. 2017 Nov 7;21(6):1481-1494. doi: 10.1016/j.celrep.2017.10.038. Link to article on publisher's site
Labbadia J, Brielmann RM, Neto MF, Lin Y, Haynes CM, Morimoto RI. (2017). Mitochondrial Stress Restores the Heat Shock Response and Prevents Proteostasis Collapse during Aging. UMass Metabolic Network Publications. https://doi.org/10.1016/j.celrep.2017.10.038. Retrieved from https://escholarship.umassmed.edu/metnet_pubs/145
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