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

Chiara Galber; Giovanni Minervini; Giuseppe Cannino; Francesco Boldrin; Valeria Petronilli; Silvio Tosatto; Giovanna Lippe; Valentina Giorgio

doi:10.1016/j.celrep.2021.109111

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

Cell Rep. 2021 May 11;35(6):109111. doi: 10.1016/j.celrep.2021.109111.

Authors

Chiara Galber¹, Giovanni Minervini², Giuseppe Cannino², Francesco Boldrin³, Valeria Petronilli¹, Silvio Tosatto², Giovanna Lippe⁴, Valentina Giorgio⁵

Affiliations

¹ Department of Biomedical Sciences, University of Padova, Padova 35121, Italy; Consiglio Nazionale delle Ricerche Institute of Neuroscience, Padova 35121, Italy.
² Department of Biomedical Sciences, University of Padova, Padova 35121, Italy.
³ Department of Biology, University of Padova, Padova 35121, Italy.
⁴ Department of Medicine, University of Udine, Udine 33100, Italy.
⁵ 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.

PMID: 33979610
DOI: 10.1016/j.celrep.2021.109111

Abstract

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.

Keywords: ATP synthase; f subunit; mitochondrial morphology; permeability transition pore, PTP.

Publication types

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

MeSH terms

HeLa Cells
Humans
Mitochondria / metabolism*
Mitochondrial Proton-Translocating ATPases / metabolism*
Permeability

Substances

Mitochondrial Proton-Translocating ATPases