PUBLICATION
The Unique Cysteine of F-ATP Synthase OSCP Subunit Participates in Modulation of the Permeability Transition Pore
- Authors
- Carraro, M., Jones, K., Sartori, G., Schiavone, M., Antonucci, S., Kucharczyk, R., di Rago, J.P., Franchin, C., Arrigoni, G., Forte, M., Bernardi, P.
- ID
- ZDB-PUB-200904-12
- Date
- 2020
- Source
- Cell Reports 32: 108095 (Journal)
- Registered Authors
- Schiavone, Marco
- Keywords
- F-ATP synthase, OSCP, cyclophilin D, cysteine, mitochondria, oxidation, permeability transition pore
- MeSH Terms
-
- Cysteine/metabolism*
- Humans
- Mitochondrial Permeability Transition Pore/metabolism*
- Mitochondrial Proton-Translocating ATPases/metabolism*
- Permeability*
- PubMed
- 32877677 Full text @ Cell Rep.
Citation
Carraro, M., Jones, K., Sartori, G., Schiavone, M., Antonucci, S., Kucharczyk, R., di Rago, J.P., Franchin, C., Arrigoni, G., Forte, M., Bernardi, P. (2020) The Unique Cysteine of F-ATP Synthase OSCP Subunit Participates in Modulation of the Permeability Transition Pore. Cell Reports. 32:108095.
Abstract
The mitochondrial permeability transition pore (PTP) is a Ca2+-activated channel that plays a key role in cell death. Thiol oxidation facilitates PTP opening, yet the targets and molecular mechanisms still await a definition. Here, we investigate the role of C141 of F-ATP synthase oligomycin sensitivity conferral protein (OSCP) subunit in PTP modulation by oxidation. We find that the OSCP C141S mutation confers resistance to PTP opening and cell death by diamide and MitoParaquat only when cyclophilin D (CyPD) has been ablated, a protective role that can be explained by CyPD shielding C141 from oxidants. The mutation decreases apoptosis in zebrafish embryos, indicating that this OSCP residue is involved in development. Site-directed mutagenesis in yeast suggests that other conserved cysteines in the α, γ, and c subunits of F-ATP synthase are not involved in PTP modulation. Thus, OSCP provides a strategic site that regulates PTP opening by the interplay between CyPD (un)binding and thiol oxidation-reduction.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping