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

Dec 12, 2025Nature communications

Different versions of a key protein in Caenorhabditis elegans affect growth, reproduction, stress resistance, aging, and cell cleanup

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Abstract

Knockdown of hsp-4 in Caenorhabditis elegans induces autophagy and enhances tolerance to protein aggregation stress.

  • Two homologous HSP70 chaperones, HSP-3 and HSP-4, have both overlapping and distinct functions in maintaining cell health.
  • Their activity is influenced by factors such as tissue type, age, and environmental stress.
  • HSP-3 and HSP-4 play unique roles in regulating longevity related to dietary restrictions and reduced insulin signaling.
  • The process of autophagy triggered by hsp-4 knockdown involves the receptor Sec-62 and the protein IRE-1.
  • In human cells, the release of the chaperone BiP from IRE-1 during ER stress may enhance autophagy by facilitating interaction with Sec-62.

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Key numbers

240
Gene Upregulation
Distinct genes upregulated upon HSP-4 compared to control.
83
Gene Downregulation
Distinct genes downregulated upon HSP-3 compared to control.

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