UMMS Affiliation
Department of Molecular, Cell and Cancer Biology; UMass Metabolic Network
Publication Date
2017-11-07
Document Type
Article
Disciplines
Biochemistry | Cell Biology | Cellular and Molecular Physiology | Molecular Biology
Abstract
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.
Keywords
HSF-1, aging, heat shock response, mitochondria, proteostasis, stress resistance
Rights and Permissions
© 2017 The Author(s).
DOI of Published Version
10.1016/j.celrep.2017.10.038
Source
Cell Rep. 2017 Nov 7;21(6):1481-1494. doi: 10.1016/j.celrep.2017.10.038. Link to article on publisher's site
Journal/Book/Conference Title
Cell reports
Related Resources
PubMed ID
29117555
Repository Citation
Labbadia, Johnathan; Brielmann, Renee M.; Neto, Mario F.; Lin, Yi-Fan; Haynes, Cole M.; and Morimoto, Richard I., "Mitochondrial Stress Restores the Heat Shock Response and Prevents Proteostasis Collapse during Aging" (2017). UMass Metabolic Network Publications. 145.
https://escholarship.umassmed.edu/metnet_pubs/145
Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.
Included in
Biochemistry Commons, Cell Biology Commons, Cellular and Molecular Physiology Commons, Molecular Biology Commons