The f subunit of human ATP synthase is essential for normal mitochondrial morphology and permeability transition
| Autor: | Valentina Giorgio, Francesco Boldrin, Giuseppe Cannino, Valeria Petronilli, Chiara Galber, Silvio C. E. Tosatto, Giovanni Minervini, Giovanna Lippe |
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| Přispěvatelé: | Galber C., Minervini G., Cannino G., Boldrin F., Petronilli V., Tosatto S., Lippe G., Giorgio V. |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
permeability transition pore PTP Protein subunit PTP General Biochemistry Genetics and Molecular Biology Permeability mitochondrial morphology 03 medical and health sciences 0302 clinical medicine Downregulation and upregulation RNA interference Humans chemistry.chemical_classification Gene knockdown ATP synthase biology permeability transition pore Mitochondrial Proton-Translocating ATPases f subunit Cell biology Mitochondria Crista 030104 developmental biology Enzyme chemistry biology.protein 030217 neurology & neurosurgery ATP5J2 HeLa Cells |
| Zdroj: | Cell reports. 35(6) |
| ISSN: | 2211-1247 |
| Popis: | Summary 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. |
| Databáze: | OpenAIRE |
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