title: Control of Mitochondrial Remodeling by the ATPase Inhibitory Factor 1 Unveils a Pro-survival Relay via OPA1.
abstract: The ubiquitously expressed ATPase inhibitory factor 1 (IF1) is a mitochondrial protein that blocks the reversal of the F1Fo-ATPsynthase, preventing dissipation of cellular ATP and ischemic damage. IF1suppresses programmed cell death, enhancing tumor invasion and chemoresistance, and is expressed in various types of human cancers. In this study, we examined its effect on mitochondrial redox balance and apoptotic cristae remodeling, finding that, by maintaining ATP levels, IF1reduces glutathione (GSH) consumption and inactivation of peroxiredoxin 3 (Prx3) during apoptosis. This correlates with inhibition of metallopeptidase OMA1-mediated processing of the pro-fusion dynamin-related protein optic atrophy 1 (OPA1). Stabilization of OPA1 impedes cristae remodeling and completion of apoptosis. Taken together, these data suggest that IF1acts on both mitochondrial bioenergetics and structure, is involved in mitochondrial signaling in tumor cells, and may underlie their proliferative capacity.
authors.affiliation: Department of Comparative Biomedical Sciences, The Royal Veterinary College London and UCL Consortium for Mitochondrial Research, Royal College Street, NW1 0TU London, UK; Department of Biology, University of Rome "Tor Vergata," 00133 Rome, Italy.
authors.forename: Danilo
authors.initials: D
authors.lastname: Faccenda
authors.affiliation: Kyoto Sangyo University, Kamigamo-Motoyama, Kyoto 603-8555, Japan.
authors.forename: Junji
authors.initials: J
authors.lastname: Nakamura
authors.affiliation: Department of Comparative Biomedical Sciences, The Royal Veterinary College London and UCL Consortium for Mitochondrial Research, Royal College Street, NW1 0TU London, UK.
authors.forename: Giulia
authors.initials: G
authors.lastname: Gorini
authors.affiliation: Department of Comparative Biomedical Sciences, The Royal Veterinary College London and UCL Consortium for Mitochondrial Research, Royal College Street, NW1 0TU London, UK.
authors.forename: Gurtej K
authors.initials: GK
authors.lastname: Dhoot
authors.affiliation: Department of Biology, University of Rome "Tor Vergata," 00133 Rome, Italy; National Institute for Infectious Diseases, IRCCS "Lazzaro Spallanzani," Rome, Italy.
authors.forename: Mauro
authors.initials: M
authors.lastname: Piacentini
authors.affiliation: Kyoto Sangyo University, Kamigamo-Motoyama, Kyoto 603-8555, Japan.
authors.forename: Masusuke
authors.initials: M
authors.lastname: Yoshida
authors.affiliation: Department of Comparative Biomedical Sciences, The Royal Veterinary College London and UCL Consortium for Mitochondrial Research, Royal College Street, NW1 0TU London, UK; Department of Biology, University of Rome "Tor Vergata," 00133 Rome, Italy. Electronic address: mcampanella@rvc.ac.uk.
authors.forename: Michelangelo
authors.initials: M
authors.lastname: Campanella
mesh_terms: D000251:Adenosine Triphosphatases / Q000378:metabolism*; D000818:Animals; D017209:Apoptosis / Q000502:physiology; D002460:Cell Line; D045744:Cell Line, Tumor; D004734:Energy Metabolism / Q000502:physiology; D020558:GTP Phosphohydrolases / Q000378:metabolism*; D005978:Glutathione / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D008666:Metalloendopeptidases / Q000378:metabolism; D051379:Mice; D008928:Mitochondria / Q000378:metabolism* / Q000502:physiology*; D051336:Mitochondrial Membranes / Q000378:metabolism; D024101:Mitochondrial Proteins / Q000378:metabolism; D011506:Proteins / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D000097795:ATPase Inhibitory Protein
chemical_list: D000251:Adenosine Triphosphatases; D020558:GTP Phosphohydrolases; D005978:Glutathione; D008666:Metalloendopeptidases; D024101:Mitochondrial Proteins; D011506:Proteins; D000097795:ATPase Inhibitory Protein; C477817:molecule metalloprotease-related protein-1, human; C415198:OPA1 protein, human
keywords: IF(1); OMA1; OPA1; Prxs; ROS; cancer; mitochondria