The DOI matches its Crossref record; 229 of the 229 references it cites were found in a registry or an index.
Calcium, ATP, and ROS: a mitochondrial love-hate triangle
Abstract
The mitochondrion is at the core of cellular energy metabolism, being the site of most ATP generation. Calcium is a key regulator of mitochondrial function and acts at several levels within the organelle to stimulate ATP synthesis. However, the dysregulation of mitochondrial Ca(2+) homeostasis is now recognized to play a key role in several pathologies. For example, mitochondrial matrix Ca(2+) overload can lead to enhanced generation of reactive oxygen species, triggering of the permeability transition pore, and cytochrome c release, leading to apoptosis. Despite progress regarding the independent roles of both Ca(2+) and mitochondrial dysfunction in disease, the molecular mechanisms by which Ca(2+) can elicit mitochondrial dysfunction remain elusive. This review highlights the delicate balance between the positive and negative effects of Ca(2+) and the signaling events that perturb this balance. Overall, a "two-hit" hypothesis is developed, in which Ca(2+) plus another pathological stimulus can bring about mitochondrial dysfunction.
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In the citing paper
“Peroxides produced by mitochondria can create nonenzymatic shunts in the TCA cycle (56, 121).”
From Mitochondrial reactive oxygen species production in excitable cells: Modulators of mitochondrial and cell function (2009) · cites this paper as [56]
In the citing paper
“In turn, an increased Ca 2ϩ load in the mitochondrial matrix has been linked to increased ROS production and increased permeability transition pore opening, leading to apoptosis (40,45).”
From Simvastatin Effects on Skeletal Muscle (2013) · cites this paper as [45]
Citations
Cites
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A role for mitochondria in nlrp3 inflammasome activation
Zhou, R., Yazdi, A. S., Menu, P., & Tschopp, J. (2011) · Nature · doi:10.1038/nature09663 · Cited by 5,602
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Xia, T., Kovochich, M., Brant, J. A., Hotze, M., Sempf, J. M., Oberley, T. D., Sioutas, C., Yeh, J. I., Wiesner, M. R., & Nel, A. E. (2006) · Nano Letters · doi:10.1021/nl061025k · Cited by 1,931
Hallmarks of neurodegenerative diseases
Wilson, D. M., Cookson, M. R., Van Den Bosch, L., Zetterberg, H., Holtzman, D. M., & Dewachter, I. (2023) · Cell · doi:10.1016/j.cell.2022.12.032 · Cited by 1,789
Calcium and ROS: A mutual interplay
Görlach, A., Bertram, K., Hudecova, S., & Krizanova, O. (2015) · Redox Biology · doi:10.1016/j.redox.2015.08.010 · Cited by 1,546
Metadata
- Authors
- Brookes, P. S., Yoon, Y., Robotham, J. L., Anders, M. W., & Sheu, S.-S.
- Affiliations
- University of Rochester Medicine (US)
- Venue
- American Journal of Physiology-Cell Physiology
- Publisher
- American Physiological Society
- Published
- 2004-10
- Volume
- 287
- Issue
- 4
- Pages
- C817-C833
- ISSN
- 0363-6143 (ISSN-L)
- 1522-1563
- OpenAlex
- W2068048197
- Cited by
- 2,575
- References
- 227
- Citations by year
- 2026: 72 · 2025: 112 · 2024: 126 · 2023: 138 · 2022: 144 · 2021: 177 · 2020: 162 · 2019: 134 · 2018: 125 · 2017: 125 · 2016: 122 · 2015: 125 · 2014: 124 · 2013: 129 · 2012: 124
- FWCI
- 5.61
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- American Journal of Physiology-Cell Physiology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Medical Center, University of Rochester
- National Heart, Lung, and Blood Institute (HL 33333, R01HL033333, HL-71158-01, R01HL071158)
- National Institute of Diabetes and Digestive and Kidney Diseases (DK-061991, R01DK061991)
- National Institute of Neurological Disorders and Stroke (NS-37710, R01NS037710)
- 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 › Cell Biology › Autophagy in Disease and Therapy
- Keywords
- mitochondrial calcium homeostasis, ATP production, reactive oxygen species, mitochondrial dysfunction, mitochondrial permeability transition pore, cytochrome c release, apoptosis, two-hit hypothesis, mitochondrial bioenergetics, calcium signaling
- MeSH terms
- Adenosine Triphosphate, Calcium, Energy Metabolism, Ion Channels, Mitochondria, Signal Transduction, Reactive Oxygen Species
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