Role of the c subunit of the FO ATP synthase in mitochondrial permeability transition
- PMID: 23343770
- PMCID: PMC3594268
- DOI: 10.4161/cc.23599
Role of the c subunit of the FO ATP synthase in mitochondrial permeability transition
Abstract
The term "mitochondrial permeability transition" (MPT) refers to an abrupt increase in the permeability of the inner mitochondrial membrane to low molecular weight solutes. Due to osmotic forces, MPT is paralleled by a massive influx of water into the mitochondrial matrix, eventually leading to the structural collapse of the organelle. Thus, MPT can initiate mitochondrial outer membrane permeabilization (MOMP), promoting the activation of the apoptotic caspase cascade as well as of caspase-independent cell death mechanisms. MPT appears to be mediated by the opening of the so-called "permeability transition pore complex" (PTPC), a poorly characterized and versatile supramolecular entity assembled at the junctions between the inner and outer mitochondrial membranes. In spite of considerable experimental efforts, the precise molecular composition of the PTPC remains obscure and only one of its constituents, cyclophilin D (CYPD), has been ascribed with a crucial role in the regulation of cell death. Conversely, the results of genetic experiments indicate that other major components of the PTPC, such as voltage-dependent anion channel (VDAC) and adenine nucleotide translocase (ANT), are dispensable for MPT-driven MOMP. Here, we demonstrate that the c subunit of the FO ATP synthase is required for MPT, mitochondrial fragmentation and cell death as induced by cytosolic calcium overload and oxidative stress in both glycolytic and respiratory cell models. Our results strongly suggest that, similar to CYPD, the c subunit of the FO ATP synthase constitutes a critical component of the PTPC.
Keywords: ATP5G1; apoptosis; caspases; cytochrome c; mitochondrial respiratory chain; p53; permeability transition pore (PTP).
Figures
![None](https://cdn.statically.io/img/www.ncbi.nlm.nih.gov/pmc/articles/instance/3594268/bin/cc-12-674-g1.gif)
![None](https://cdn.statically.io/img/www.ncbi.nlm.nih.gov/pmc/articles/instance/3594268/bin/cc-12-674-g2.gif)
![None](https://cdn.statically.io/img/www.ncbi.nlm.nih.gov/pmc/articles/instance/3594268/bin/cc-12-674-g3.gif)
Similar articles
-
Permeability transition in human mitochondria persists in the absence of peripheral stalk subunits of ATP synthase.Proc Natl Acad Sci U S A. 2017 Aug 22;114(34):9086-9091. doi: 10.1073/pnas.1711201114. Epub 2017 Aug 7. Proc Natl Acad Sci U S A. 2017. PMID: 28784775 Free PMC article.
-
Mitochondrial permeability transition involves dissociation of F1FO ATP synthase dimers and C-ring conformation.EMBO Rep. 2017 Jul;18(7):1077-1089. doi: 10.15252/embr.201643602. Epub 2017 May 31. EMBO Rep. 2017. PMID: 28566520 Free PMC article.
-
Molecular mechanisms of cell death: central implication of ATP synthase in mitochondrial permeability transition.Oncogene. 2015 Mar 19;34(12):1475-86. doi: 10.1038/onc.2014.96. Epub 2014 Apr 14. Oncogene. 2015. PMID: 24727893 Review.
-
Voltage-dependent anion channels are dispensable for mitochondrial-dependent cell death.Nat Cell Biol. 2007 May;9(5):550-5. doi: 10.1038/ncb1575. Epub 2007 Apr 8. Nat Cell Biol. 2007. PMID: 17417626 Free PMC article.
-
Role of the mitochondrial membrane permeability transition in cell death.Apoptosis. 2007 May;12(5):835-40. doi: 10.1007/s10495-006-0525-7. Apoptosis. 2007. PMID: 17136322 Review.
Cited by
-
Peptides Targeting the IF1-ATP Synthase Complex Modulate the Permeability Transition Pore in Cancer HeLa Cells.Int J Mol Sci. 2024 Apr 25;25(9):4655. doi: 10.3390/ijms25094655. Int J Mol Sci. 2024. PMID: 38731874 Free PMC article.
-
Mitochondrial Permeability Transition, Cell Death and Neurodegeneration.Cells. 2024 Apr 8;13(7):648. doi: 10.3390/cells13070648. Cells. 2024. PMID: 38607087 Free PMC article. Review.
-
Biophysical interplay between extracellular matrix remodeling and hypoxia signaling in regulating cancer metastasis.Front Cell Dev Biol. 2024 Mar 13;12:1335636. doi: 10.3389/fcell.2024.1335636. eCollection 2024. Front Cell Dev Biol. 2024. PMID: 38544822 Free PMC article. Review.
-
Differential Expression of Nuclear-Encoded Mitochondrial Protein Genes of ATP Synthase Across Different Tissues of Female Buffalo.Mol Biotechnol. 2024 Feb 2. doi: 10.1007/s12033-024-01085-x. Online ahead of print. Mol Biotechnol. 2024. PMID: 38305843
-
The mitochondrial ATP synthase is a negative regulator of the mitochondrial permeability transition pore.Proc Natl Acad Sci U S A. 2023 Dec 19;120(51):e2303713120. doi: 10.1073/pnas.2303713120. Epub 2023 Dec 13. Proc Natl Acad Sci U S A. 2023. PMID: 38091291 Free PMC article.
References
-
- Kroemer G, Galluzzi L, Vandenabeele P, Abrams J, Alnemri ES, Baehrecke EH, et al. Nomenclature Committee on Cell Death 2009 Classification of cell death: recommendations of the Nomenclature Committee on Cell Death 2009. Cell Death Differ. 2009;16:3–11. doi: 10.1038/cdd.2008.150. - DOI - PMC - PubMed
Publication types
MeSH terms
Substances
Grants and funding
LinkOut - more resources
Full Text Sources
Other Literature Sources
Molecular Biology Databases
Research Materials
Miscellaneous