Short-form OPA1 is a molecular chaperone in mitochondrial intermembrane space

Sci China Life Sci. 2022 Feb;65(2):227-235. doi: 10.1007/s11427-021-1962-0. Epub 2021 Aug 31.

Abstract

Mitochondria, double-membrane organelles, are known to participate in a variety of metabolic and signal transduction pathways. The intermembrane space (IMS) of mitochondria is proposed to subject to multiple damages emanating from the respiratory chain. The optic atrophy 1 (OPA1), an important protein for mitochondrial fusion, is cleaved into soluble short-form (S-OPA1) under stresses. Here we report that S-OPA1 could function as a molecular chaperone in IMS. We purified the S-OPA1 (amino acid sequence after OPA1 isoform 5 S1 site) protein and showed it protected substrate proteins from thermally and chemically induced aggregation and strengthened the thermotolerance of Escherichia coli (E. coli). We also showed that S-OPA1 conferred thermotolerance on IMS proteins, e.g., neurolysin. The chaperone activity of S-OPA1 may be required for maintaining IMS homeostasis in mitochondria.

Keywords: OPA1; chaperone; heat shock; mitochondria; mitochondrial homeostasis.

MeSH terms

  • Escherichia coli / physiology
  • Escherichia coli Proteins / chemistry
  • Escherichia coli Proteins / genetics
  • Escherichia coli Proteins / metabolism
  • GTP Phosphohydrolases / chemistry
  • GTP Phosphohydrolases / genetics
  • GTP Phosphohydrolases / metabolism*
  • Homeostasis
  • Metalloendopeptidases / metabolism
  • Mitochondria / metabolism
  • Mitochondrial Membranes / metabolism*
  • Mitochondrial Proteins / metabolism
  • Molecular Chaperones / chemistry
  • Molecular Chaperones / genetics
  • Molecular Chaperones / metabolism*
  • Protein Isoforms
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism
  • Thermotolerance

Substances

  • Escherichia coli Proteins
  • Mitochondrial Proteins
  • Molecular Chaperones
  • Protein Isoforms
  • Recombinant Proteins
  • Metalloendopeptidases
  • neurolysin
  • GTP Phosphohydrolases