A 20/20 view of ANT function in mitochondrial biology and necrotic cell death
Open accessAbstract
The adenosine nucleotide translocase (ANT) family of proteins are inner mitochondrial membrane proteins involved in energy homeostasis and cell death. The primary function of ANT proteins is to exchange cytosolic ADP with matrix ATP, facilitating the export of newly synthesized ATP to the cell while providing new ADP substrate to the mitochondria. As such, the ANT proteins are central to maintaining energy homeostasis in all eukaryotic cells. Evidence also suggests that the ANTs constitute a pore-forming component of the mitochondrial permeability transition pore (MPTP), a structure that forms in the inner mitochondrial membrane that is thought to underlie regulated necrotic cell death. Additionally, emerging studies suggest that ANT proteins are also critical for mitochondrial uncoupling and for promoting mitophagy. Thus, the ANTs are multifunctional proteins that are poised to participate in several aspects of mitochondrial biology and the greater regulation of cell death, which will be discussed here.
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Some combination of mitochondrial proteins (CypD, ANT, ATP synthase, VDAC, PiC, SPG-7) is necessary to fully exhibit the properties of mPTP.
“The inescapable conclusion from these studies is that some combination of these proteins is necessary to fully exhibit the properties of mPTP [1,18,20,21].”
From The mitochondrial permeability transition: Nexus of aging, disease and longevity (2021) · cites this paper as [20]
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- Authors
- Bround, M. J., Bers, D. M., & Molkentin, J. D.
- Affiliations
- Cincinnati Children's Hospital Medical Center (US)
- University of California, Davis (US)
- Corresponding author
- Molkentin, Jeffery D.
- Venue
- Journal of Molecular and Cellular Cardiology
- Publisher
- Elsevier BV
- Published
- 2020-07
- Volume
- 144
- Pages
- A3-A13
- ISSN
- 0022-2828 (ISSN-L)
- PMC
- PMC7483807
- OpenAlex
- W3026500698
- Cited by
- 83
- References
- 176
- Citations by year
- 2026: 7 · 2025: 21 · 2024: 12 · 2023: 11 · 2022: 13 · 2021: 11 · 2020: 8
- FWCI
- 1.05
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Journal of Molecular and Cellular Cardiology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (R01-HL132831 JDM, R01-HL030077)
- American Heart Association (18POST33960216)
- National Heart, Lung, and Blood Institute
- Fondation Leducq
- Howard Hughes Medical Institute
- Topics
- 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
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › ATP Synthase and ATPases Research
- Keywords
- mitochondrial permeability transition pore, ADP/ATP exchange, mitochondrial uncoupling, mitophagy, mitochondrial inner membrane proteins
- MeSH terms
- Necroptosis, Mitochondrial Permeability Transition Pore, Mitochondrial ADP, ATP Translocases, Animals, Gene Expression Regulation, Multigene Family, Humans, Mitochondria, Models, Biological, Oxidative Phosphorylation, Mitochondrial Membrane Transport Proteins
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