Functionally diversified Caenorhabditis elegans BiP orthologs control body growth, reproduction, stress resistance, aging, and autophagy.

ABSTRACT: Cellular systems governing protein folding depend on functional redundancy and diversification to maintain proteostasis. Here, using Caenorhabditis elegans, we show two homologous ER-resident HSP70 chaperones, HSP-3 and HSP-4, have overlapping and distinct roles in ER proteostasis and organismal physiology. Their expression and function vary by tissue, age, and stress, impacting ER stress resistance, reproduction, body size, and lifespan. We also find HSP-3 and HSP-4 uniquely regulate dietary restriction and reduced insulin signaling-mediated longevity in C. elegans. Notably, knockdown of hsp-4, but not hsp-3, induces autophagy and enhances tolerance to protein aggregation stress; this process requires the ortholog of ER-Phagy receptor Sec-62 (C18E9.2) and IRE-1. Finally, human cell data s

SUBMITTER: Urban ND 

PROVIDER: S-EPMC12700872 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature