The f subunit of human ATP synthase is essential for normal mitochondrial morphology and permeability transition.


Journal

Cell reports
ISSN: 2211-1247
Titre abrégé: Cell Rep
Pays: United States
ID NLM: 101573691

Informations de publication

Date de publication:
11 05 2021
Historique:
received: 24 02 2020
revised: 11 03 2021
accepted: 20 04 2021
entrez: 12 5 2021
pubmed: 13 5 2021
medline: 10 2 2022
Statut: ppublish

Résumé

The f subunit is localized at the base of the ATP synthase peripheral stalk. Its function in the human enzyme is poorly characterized. Because full disruption of its ATP5J2 gene with the CRISPR-Cas9 strategy in the HAP1 human model has been shown to cause alterations in the amounts of other ATP synthase subunits, here we investigated the role of the f subunit in HeLa cells by regulating its levels through RNA interference. We confirm the role of the f subunit in ATP synthase dimer stability and observe that its downregulation per se does not alter the amounts of the other enzyme subunits or ATP synthase synthetic/hydrolytic activity. We show that downregulation of the f subunit causes abnormal crista organization and decreases permeability transition pore (PTP) size, whereas its re-expression in f subunit knockdown cells rescues mitochondrial morphology and PTP-dependent swelling.

Identifiants

pubmed: 33979610
pii: S2211-1247(21)00445-9
doi: 10.1016/j.celrep.2021.109111
pii:
doi:

Substances chimiques

Mitochondrial Proton-Translocating ATPases EC 3.6.3.-

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

109111

Informations de copyright

Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of interests The authors declare no competing interests.

Auteurs

Chiara Galber (C)

Department of Biomedical Sciences, University of Padova, Padova 35121, Italy; Consiglio Nazionale delle Ricerche Institute of Neuroscience, Padova 35121, Italy.

Giovanni Minervini (G)

Department of Biomedical Sciences, University of Padova, Padova 35121, Italy.

Giuseppe Cannino (G)

Department of Biomedical Sciences, University of Padova, Padova 35121, Italy.

Francesco Boldrin (F)

Department of Biology, University of Padova, Padova 35121, Italy.

Valeria Petronilli (V)

Department of Biomedical Sciences, University of Padova, Padova 35121, Italy; Consiglio Nazionale delle Ricerche Institute of Neuroscience, Padova 35121, Italy.

Silvio Tosatto (S)

Department of Biomedical Sciences, University of Padova, Padova 35121, Italy.

Giovanna Lippe (G)

Department of Medicine, University of Udine, Udine 33100, Italy.

Valentina Giorgio (V)

Department of Biomedical Sciences, University of Padova, Padova 35121, Italy; Consiglio Nazionale delle Ricerche Institute of Neuroscience, Padova 35121, Italy; Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna 40126, Italy. Electronic address: valentina.giorgio4@unibo.it.

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Classifications MeSH