RRC ID 51518
Author Labbadia J, Brielmann RM, Neto MF, Lin YF, Haynes CM, Morimoto RI.
Title Mitochondrial Stress Restores the Heat Shock Response and Prevents Proteostasis Collapse during Aging.
Journal Cell Rep
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.
Volume 21(6)
Pages 1481-1494
Published 2017-11-7
DOI 10.1016/j.celrep.2017.10.038
PII S2211-1247(17)31485-7
PMID 29117555
PMC PMC5726777
MeSH Aging* Animals Caenorhabditis elegans / metabolism* Caenorhabditis elegans Proteins / antagonists & inhibitors Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / metabolism Cytoplasm / metabolism Electron Transport Chain Complex Proteins / antagonists & inhibitors Electron Transport Chain Complex Proteins / metabolism Heat-Shock Proteins / genetics Heat-Shock Proteins / metabolism Heat-Shock Response / genetics* Longevity Mitochondria / drug effects Mitochondria / metabolism* Protein Binding Proteostasis / physiology RNA Interference RNA Polymerase II / genetics RNA Polymerase II / metabolism RNA, Small Interfering / metabolism Reactive Oxygen Species / metabolism Stress, Physiological Temperature Transcription Factors / genetics Transcription Factors / metabolism Xenobiotics / pharmacology
IF 8.109
Times Cited 34
C.elegans tm4525