USP-48 enables insulin-mediated longevity and modulates the mitochondrial stress response.
USP-48 is essential for insulin-mediated lifespan extension in C. elegans by regulating mitochondrial stress responses and histone H2B deubiquitination.
- Why it matters: Understanding how mitochondrial stress responses influence aging can reveal targets for promoting longevity, especially under altered insulin signaling conditions.
- What they did: A genome-wide double-RNAi screen identified USP-48 as a key regulator of the mitochondrial unfolded protein response (UPR mt), particularly required for lifespan extension in daf-2 mutants, with tissue-specific roles in the hypodermis.
- The result: USP-48 modulates mitochondrial structure and function through histone H2B deubiquitination, enabling stress-responsive gene regulation and highlighting ubiquitination as a crucial factor in metabolism-dependent aging.