MilliporeSigma
  • Home
  • Search Results
  • A Mitochondrial Stress-Specific Form of HSF1 Protects against Age-Related Proteostasis Collapse.

A Mitochondrial Stress-Specific Form of HSF1 Protects against Age-Related Proteostasis Collapse.

Developmental cell (2020-08-01)
Rhianna Williams, Mihails Laskovs, Rebecca I Williams, Ananya Mahadevan, John Labbadia
ABSTRACT

The loss of protein homeostasis (proteostasis) is a primary driver of age-related tissue dysfunction. Recent studies have revealed that the failure of proteostasis with age is triggered by developmental and reproductive cues that repress the activity of proteostasis-related pathways in early adulthood. In Caenorhabditis elegans, reduced mitochondrial electron transport chain (ETC) function during development can override signals that promote proteostasis collapse in aged tissues. However, it is unclear precisely how these beneficial effects are mediated. Here, we reveal that in response to ETC impairment, the PP2A complex generates a dephosphorylated, mitochondrial stress-specific variant of the transcription factor HSF-1. This results in the selective induction of small heat shock proteins in adulthood, thereby protecting against age-related proteostasis collapse. We propose that mitochondrial signals early in life can protect the aging cytosolic proteome by tailoring HSF-1 activity to preferentially drive the expression of non-ATP-dependent chaperones.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Methyl viologen dichloride hydrate, 98%
Sigma-Aldrich
Rotenone, ≥95%
Sigma-Aldrich
Anti-PP2A Antibody, C subunit, clone 1D6, clone 1D6, Upstate®, from mouse
Sigma-Aldrich
Monoclonal Anti-α-Tubulin antibody produced in mouse, ascites fluid, clone B-5-1-2
Roche
Anti-GFP, from mouse IgG1κ (clones 7.1 and 13.1)