Permeability transition in human mitochondria persists in the absence of peripheral stalk subunits of ATP synthase
Open accessAbstract
Significance: Mitochondria generate the cellular fuel ATP to sustain complex life. Production of ATP depends on the oxidation of energy-rich compounds to produce a chemical potential difference for hydrogen ions, the proton motive force (pmf), across the inner mitochondrial membrane (IMM). Disruption of the IMM, dissipation of the pmf, and cell death occur if the concentration of calcium ions inside mitochondria is sufficiently elevated to open a pore in the IMM. The identity of the pore is disputed. One proposal is that the pore is in the enzyme that makes ATP. Here, we show that proteins in the enzyme’s peripheral stalk are not involved in the formation or regulation of the pore.
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Very recent findings seem to exclude possibility that F1FO ATPase constitutes pore-forming component of PTPC.
“However, very recent findings seem to exclude the possibility that the F1FO ATPase constitutes the pore-forming component of the PTPC [402–405].”
From Molecular mechanisms of cell death: recommendations of the nomenclature committee on cell death 2018. (2018) · cites this paper as [405]
Cells lacking ATP5O or membrane domain of b subunit of F1FO ATP synthase appear to preserve normal PTPC activity.
“Finally, cells lacking ATP synthase, H+ transporting, mitochondrial F1 complex, O subunit (ATP5O; best known as OSCP), or the membrane domain of the b subunit of the F1FO ATP synthase (encoded by ATP5F1) appear to preserve normal PTPC activity [405].”
From Molecular mechanisms of cell death: recommendations of the nomenclature committee on cell death 2018. (2018) · cites this paper as [405]
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Self-citation
- Authors
- He, J., Carroll, J., Ding, S., Fearnley, I. M., & Walker, J. E.
- Affiliations
- University of Cambridge (GB)
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2017-08-07
- Volume
- 114
- Issue
- 34
- Pages
- 9086-9091
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC5576841
- OpenAlex
- W2744604441
- Cited by
- 182
- References
- 43
- Citations by year
- 2026: 8 · 2025: 9 · 2024: 4 · 2023: 19 · 2022: 10 · 2021: 27 · 2020: 38 · 2019: 30 · 2018: 32 · 2017: 5
- FWCI
- 11.73
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Apollo (University of Cambridge) (submittedVersion)
- Apollo
- Funders
- RCUK | Medical Research Council (MR/M009858/1)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › ATP Synthase and ATPases Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
- Keywords
- mitochondrial permeability transition, ATP synthase, mitochondrial calcium uptake, proton motive force, inner mitochondrial membrane, ATP production, human mitochondria
- MeSH terms
- Peptidyl-Prolyl Isomerase F, Mitochondrial Permeability Transition Pore, Adenosine Triphosphatases, Base Sequence, Calcium, Carrier Proteins, Humans, Membrane Proteins, Mitochondria, Mutation, Permeability, Protein Binding, Sequence Homology, Nucleic Acid, Cyclosporine, Catalytic Domain, Protein Subunits, Cyclophilins, Mitochondrial Proton-Translocating ATPases, Mitochondrial Membrane Transport Proteins, Cell Line, Tumor, Mitochondrial Membranes
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