Stress response silencing by an E3 ligase mutated in neurodegeneration.

ABSTRACT: Stress response pathways detect and alleviate adverse conditions to safeguard cell and tissue homeostasis, yet their prolonged activation induces apoptosis and disrupts organismal health^1-3. How stress responses are turned off at the right time and place remains poorly understood. Here we report a ubiquitin-dependent mechanism that silences the cellular response to mitochondrial protein import stress. Crucial to this process is the silencing factor of the integrated stress response (SIFI), a large E3 ligase complex mutated in ataxia and in early-onset dementia that degrades both unimported mitochondrial precursors and stress response components. By recognizing bifunctional substrate motifs that equally encode protein localization and stability, the SIFI complex turns off a gener

SUBMITTER: Haakonsen DL 

PROVIDER: S-EPMC10881396 | biostudies-literature | 2024 Feb

REPOSITORIES: biostudies-literature