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. IF1 suppresses 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, IF1 reduces 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 IF1 acts on both mitochondrial bioenergetics and structure, is involved in mitochondrial signaling in tumor cells, and may underlie their proliferative capacity.

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peroxiredoxin 3 profusion dynaminrelated protein optic glutathione metallopeptidase oma1mediated processing mitochondrial redox balance proliferative capacity ischemic programmed cell death apoptotic cristae remodeling reversal of the f1foatpsynthase opa1 impedes cristae consumption apoptosis atpase inhibitory factor tumor invasion mitochondrial bioenergetics

Danilo Faccenda,Junji Nakamura,Giulia Gorini,Gurtej K. Dhoot,Mauro Piacentini,Masusuke Yoshida,Michelangelo Campanella,.Control of Mitochondrial Remodeling by the ATPase Inhibitory Factor 1 Unveils a Pro-survival Relay via OPA1. 18 (8),.

Danilo Faccenda,Junji Nakamura,Giulia Gorini,Gurtej K. Dhoot,Mauro Piacentini,Masusuke Yoshida,Michelangelo Campanella,"Control of Mitochondrial Remodeling by the ATPase Inhibitory Factor 1 Unveils a Pro-survival Relay via OPA1" 18

Danilo Faccenda,Junji Nakamura,Giulia Gorini,Gurtej K. Dhoot,Mauro Piacentini,Masusuke Yoshida,Michelangelo Campanella,"Control of Mitochondrial Remodeling by the ATPase Inhibitory Factor 1 Unveils a Pro-survival Relay via OPA1"