The DOI matches its Crossref record; 29 of the 29 references it cites were found in a registry or an index.
Mitochondria, OxPhos, and neurodegeneration: cells are not just running out of gas
Open accessAbstract
Mitochondrial respiratory deficiencies have been observed in numerous neurodegenerative disorders, such as Alzheimer's and Parkinson's diseases. For decades, these reductions in oxidative phosphorylation (OxPhos) have been presumed to trigger an overall bioenergetic crisis in the neuron, resulting in cell death. While the connection between respiratory defects and neuronal death has never been proven, this hypothesis has been supported by the detection of nonspecific mitochondrial DNA mutations in these disorders. These findings led to the notion that mitochondrial respiratory defects could be initiators of these common neurodegenerative disorders, instead of being consequences of a prior insult, a theory we believe to be misconstrued. Herein, we review the roots of this mitochondrial hypothesis and offer a new perspective wherein mitochondria are analyzed not only from the OxPhos point of view, but also as a complex organelle residing at the epicenter of many metabolic pathways.
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Cites
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Cited by
Mitochondrial calcium exchange in physiology and disease
Garbincius, J. F., & Elrod, J. W. (2022) · Physiological Reviews · doi:10.1152/physrev.00041.2020 · Cited by 412
The roles of mitochondria in global and local intracellular calcium signalling
Cartes-Saavedra, B., Ghosh, A., & Hajnóczky, G. (2025) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-024-00820-1 · Cited by 126
Sancandi, M., Uysal-Onganer, P., Kraev, I., Mercer, A., & Lange, S. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21082743 · Cited by 41
“While oxidative stress has been shown to play significant roles both in the onset and progression of PD [40], it still remains open to debate whether the mitochondrial respiratory deficiencies observed in a range of neurodegenerative disorders are initiators or consequences of prior insult [41].”
BackgroundThe link between Mitochondria and Sarcopenia
Kamarulzaman, N. T., & Makpol, S. (2025) · Journal of Physiology and Biochemistry · doi:10.1007/s13105-024-01062-7 · Cited by 33
Evaluating genomic signatures of aging in brain tissue as it relates to Alzheimer’s disease
Lynch, M. T., Taub, M. A., Farfel, J. M., Yang, J., Abadir, P., De Jager, P. L., Grodstein, F., Bennett, D. A., & Mathias, R. A. (2023) · Scientific Reports · doi:10.1038/s41598-023-41400-1 · Cited by 10
Metadata
- Authors
- Area-Gomez, E., Guardia-Laguarta, C., Schon, E. A., & Przedborski, S.
- Venue
- Journal of Clinical Investigation
- Published
- 2019-01-02
- Volume
- 129
- Issue
- 1
- Pages
- 34-45
- ISSN
- 0021-9738 (ISSN-L)
- 1558-8238
- OpenAlex
- W2908362631
- Cited by
- 164
- References
- 29
- FWCI
- 5.01
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Area-Gomez, E., Guardia-Laguarta, C., Schon, E. A., & Przedborski, S. (2019). Mitochondria, OxPhos, and neurodegeneration: cells are not just running out of gas. Journal of Clinical Investigation. https://doi.org/10.1172/jci120848
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