Mitochondria regulate intracellular coenzyme Q transport and ferroptotic resistance via STARD7.
Journal
Nature cell biology
ISSN: 1476-4679
Titre abrégé: Nat Cell Biol
Pays: England
ID NLM: 100890575
Informations de publication
Date de publication:
02 2023
02 2023
Historique:
received:
04
05
2022
accepted:
06
12
2022
pubmed:
20
1
2023
medline:
17
2
2023
entrez:
19
1
2023
Statut:
ppublish
Résumé
Coenzyme Q (or ubiquinone) is a redox-active lipid that serves as universal electron carrier in the mitochondrial respiratory chain and antioxidant in the plasma membrane limiting lipid peroxidation and ferroptosis. Mechanisms allowing cellular coenzyme Q distribution after synthesis within mitochondria are not understood. Here we identify the cytosolic lipid transfer protein STARD7 as a critical factor of intracellular coenzyme Q transport and suppressor of ferroptosis. Dual localization of STARD7 to the intermembrane space of mitochondria and the cytosol upon cleavage by the rhomboid protease PARL ensures the synthesis of coenzyme Q in mitochondria and its transport to the plasma membrane. While mitochondrial STARD7 preserves coenzyme Q synthesis, oxidative phosphorylation function and cristae morphogenesis, cytosolic STARD7 is required for the transport of coenzyme Q to the plasma membrane and protects against ferroptosis. A coenzyme Q variant competes with phosphatidylcholine for binding to purified STARD7 in vitro. Overexpression of cytosolic STARD7 increases ferroptotic resistance of the cells, but limits coenzyme Q abundance in mitochondria and respiratory cell growth. Our findings thus demonstrate the need to coordinate coenzyme Q synthesis and cellular distribution by PARL-mediated STARD7 processing and identify PARL and STARD7 as promising targets to interfere with ferroptosis.
Identifiants
pubmed: 36658222
doi: 10.1038/s41556-022-01071-y
pii: 10.1038/s41556-022-01071-y
pmc: PMC9928583
doi:
Substances chimiques
Ubiquinone
1339-63-5
Carrier Proteins
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
246-257Commentaires et corrections
Type : CommentIn
Informations de copyright
© 2023. The Author(s).
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