Small heat shock proteins operate as molecular chaperones in the mitochondrial intermembrane space.
Journal
Nature cell biology
ISSN: 1476-4679
Titre abrégé: Nat Cell Biol
Pays: England
ID NLM: 100890575
Informations de publication
Date de publication:
03 2023
03 2023
Historique:
received:
20
10
2021
accepted:
12
12
2022
pubmed:
24
1
2023
medline:
17
3
2023
entrez:
23
1
2023
Statut:
ppublish
Résumé
Mitochondria are complex organelles with different compartments, each harbouring their own protein quality control factors. While chaperones of the mitochondrial matrix are well characterized, it is poorly understood which chaperones protect the mitochondrial intermembrane space. Here we show that cytosolic small heat shock proteins are imported under basal conditions into the mitochondrial intermembrane space, where they operate as molecular chaperones. Protein misfolding in the mitochondrial intermembrane space leads to increased recruitment of small heat shock proteins. Depletion of small heat shock proteins leads to mitochondrial swelling and reduced respiration, while aggregation of aggregation-prone substrates is countered in their presence. Charcot-Marie-Tooth disease-causing mutations disturb the mitochondrial function of HSPB1, potentially linking previously observed mitochondrial dysfunction in Charcot-Marie-Tooth type 2F to its role in the mitochondrial intermembrane space. Our results reveal that small heat shock proteins form a chaperone system that operates in the mitochondrial intermembrane space.
Identifiants
pubmed: 36690850
doi: 10.1038/s41556-022-01074-9
pii: 10.1038/s41556-022-01074-9
pmc: PMC10014586
doi:
Substances chimiques
Heat-Shock Proteins, Small
0
Molecular Chaperones
0
Mitochondrial Proteins
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
467-480Informations de copyright
© 2023. The Author(s).
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