InsP3R signaling mediates mitochondrial stress-induced longevity through actomyosin-dependent mitochondrial dynamics.

ABSTRACT: Certain forms of mitochondrial impairment confer longevity, while mitochondrial dysfunction arising from aging and disease-associated mutations triggers severe pathogenesis. The adaptive pathways that distinguish benefit from pathology remain unclear. Here we reveal that longevity induced by mitochondrial Complex I/ nuo-6 mutation in C. elegans is dependent on the endoplasmic reticulum (ER) Ca ²⁺ channel, InsP3R. We find that the InsP3R promotes mitochondrial respiration, but the mitochondrial calcium uniporter is dispensable for both respiration and lifespan extension in Complex I mutants, suggesting InsP3R action is independent of matrix Ca ²⁺ flux. Transcriptomic profiling and imaging reveal a previously unrecognized role for the InsP3R in regulating

SUBMITTER: Feng G 

PROVIDER: S-EPMC12424781 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature