Mitochondria, OxPhos, and neurodegeneration: cells are not just running out of gas
Estela Area-Gomez,1 Cristina Guardia-Laguarta,2 Eric A. Schon,1,3 and Serge Przedborski2
1Department of Neurology,
2Department of Pathology and Cell Biology, and
3Department of Genetics and Development, Columbia University Medical Center, New York, New York, USA.
Address correspondence to: Serge Przedborski, Department of Pathology and Cell Biology, Columbia University Medical Center, 630 West 168th Street, New York, New York 10032, USA. Phone: 212.342.4119; Email: sp30@cumc.columbia.edu.
Find articles by Area-Gomez, E. in: JCI | PubMed | Google Scholar
1Department of Neurology,
2Department of Pathology and Cell Biology, and
3Department of Genetics and Development, Columbia University Medical Center, New York, New York, USA.
Address correspondence to: Serge Przedborski, Department of Pathology and Cell Biology, Columbia University Medical Center, 630 West 168th Street, New York, New York 10032, USA. Phone: 212.342.4119; Email: sp30@cumc.columbia.edu.
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1Department of Neurology,
2Department of Pathology and Cell Biology, and
3Department of Genetics and Development, Columbia University Medical Center, New York, New York, USA.
Address correspondence to: Serge Przedborski, Department of Pathology and Cell Biology, Columbia University Medical Center, 630 West 168th Street, New York, New York 10032, USA. Phone: 212.342.4119; Email: sp30@cumc.columbia.edu.
Find articles by Schon, E. in: JCI | PubMed | Google Scholar
1Department of Neurology,
2Department of Pathology and Cell Biology, and
3Department of Genetics and Development, Columbia University Medical Center, New York, New York, USA.
Address correspondence to: Serge Przedborski, Department of Pathology and Cell Biology, Columbia University Medical Center, 630 West 168th Street, New York, New York 10032, USA. Phone: 212.342.4119; Email: sp30@cumc.columbia.edu.
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Przedborski, S.
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First published January 2, 2019 - More info
J Clin Invest. 2019;129(1):34–45. https://doi.org/10.1172/JCI120848.
Copyright © 2019, American Society for Clinical Investigation
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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