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Updated: Jun 19, 2026
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Oxygen-Independent Assays to Measure Mitochondrial Function in Mammals
Published on: May 19, 2023
Mitochondria and hypoxic signaling: a new view
Robert O Poyton1, Pablo R Castello, Kerri A Ball
1Department of Molecular, Cellular, and Developmental Biology, University of Colorado, Boulder, CO 80309, USA. Robert.Poyton@colorado.edu
Annals of the New York Academy of Sciences
|October 23, 2009
Summary
Mitochondria generate nitric oxide (NO) during low oxygen conditions, a process dependent on nitrite and cytochrome c oxidase. This discovery offers a new model for hypoxic signaling in eukaryotic cells.
Area of Science:
- Cellular Biology
- Biochemistry
- Molecular Biology
Background:
- Eukaryotic cells regulate gene expression in response to low oxygen (hypoxia).
- The mitochondrial respiratory chain is implicated in oxygen-regulated gene expression.
- The precise role of mitochondria in hypoxic signaling has remained unclear.
Purpose of the Study:
- To investigate the role of mitochondria in hypoxic signaling.
- To elucidate the mechanism by which mitochondria respond to and influence cellular responses to low oxygen.
- To propose a novel model for hypoxic signaling involving mitochondrial function.
Main Methods:
- Investigated mitochondrial nitric oxide (NO) production under oxygen-limiting conditions.
- Characterized the requirements for NO production, including nitrite dependence, electron donors, and pH.
- Assessed the release of mitochondrially produced NO from cells.
Main Results:
- Mitochondria were found to produce nitric oxide (NO) when oxygen becomes limiting.
- This NO production is dependent on nitrite (NO2-) and requires an electron donor.
- The activity, termed Cco/NO*, is mediated by cytochrome c oxidase in a pH-dependent manner.
- A portion of the produced NO is released extracellularly, suggesting a role in intercellular signaling.
Conclusions:
- Mitochondria play a direct role in hypoxic signaling through the production of nitric oxide.
- A novel mechanism, Cco/NO*, involving cytochrome c oxidase explains mitochondrial NO generation under hypoxia.
- Mitochondrially generated NO may function in both intracellular and extracellular hypoxic signaling pathways.
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