Mitochondrial unfolded-protein response (UPRmt)

Definition

Category: Stress-signalling pathway

Also known as: UPRmt, mitochondrial stress response

The UPRmt is a stress response that detects mitochondrial protein-folding imbalance and triggers a transcriptional programme (via ATFS-1 in C. elegans, ATF5 in mammals) to restore proteostasis. In model organisms, moderate UPRmt activation is linked to extended lifespan (mitohormesis); its role in mammalian aging is far less settled.

Key points

• The lifespan link is strongest in invertebrate models (C. elegans); extrapolation to human aging is speculative.
• UPRmt is one route by which mild mitochondrial stress can be net-beneficial (mitohormesis).
• This is a mechanism-context node: no intervention on this site is an established UPRmt-targeting human therapy.

Sourcing

Standard UPRmt reviews (Haynes; Auwerx lab model-organism work). Review-level description.

Reference synthesis (tier 4); verification: review_level_2026-07-12.