Mitochondrial Stress Restores the Heat Shock Response and Prevents Proteostasis Collapse during Aging
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Authors
Labbadia, JohnathanBrielmann, Renee M.
Neto, Mario F.
Lin, Yi-Fan
Haynes, Cole M.
Morimoto, Richard I.
Document Type
Journal ArticlePublication Date
2017-11-07Keywords
HSF-1aging
heat shock response
mitochondria
proteostasis
stress resistance
Biochemistry
Cell Biology
Cellular and Molecular Physiology
Molecular Biology
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Show full item recordAbstract
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.Source
Cell Rep. 2017 Nov 7;21(6):1481-1494. doi: 10.1016/j.celrep.2017.10.038. Link to article on publisher's siteDOI
10.1016/j.celrep.2017.10.038Permanent Link to this Item
http://hdl.handle.net/20.500.14038/36627PubMed ID
29117555Related Resources
Link to Article in PubMedRights
© 2017 The Author(s).Distribution License
http://creativecommons.org/licenses/by-nc-nd/4.0/ae974a485f413a2113503eed53cd6c53
10.1016/j.celrep.2017.10.038