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Nitrite reductase activity of cytochrome c
Swati Basu1, Natalia A Azarova, Michael D Font
1Department of Physics, Wake Forest University, Winston-Salem, North Carolina 27109, USA.
Nitrite, once thought inert, is a key signaling molecule. Researchers discovered that cytochrome c, a mitochondrial protein, can reduce nitrite to nitric oxide (NO), impacting cellular respiration and signaling.
Area of Science:
- Biochemistry
- Cellular Biology
- Physiology
Background:
- Nitrite (NO2-) is increasingly recognized as a vital signaling molecule, mediating responses like hypoxic vasodilation and cytoprotection.
- Previously considered biologically inert, nitrite is now understood to be a crucial regulator of gene and protein expression.
- Nitrite's signaling function is primarily through its reduction to nitric oxide (NO) by heme-containing proteins.
Purpose of the Study:
- To investigate the potential of mitochondrial proteins to reduce nitrite to nitric oxide (NO).
- To identify novel nitrite reductase activities within cellular respiration pathways.
- To explore the physiological implications of nitrite reduction by mitochondrial components.
Main Methods:
- Investigated the interaction between nitrite and purified cytochrome c under varying conditions.
- Utilized spectroscopic methods to detect NO production.
- Assessed the impact of NO generated by cytochrome c on mitochondrial respiration.
Main Results:
- Demonstrated that cytochrome c effectively reduces nitrite to NO under anoxic and acidic conditions.
- Showed that this nitrite reductase activity is dependent on the pentacoordination of heme iron in cytochrome c.
- Confirmed that NO generated by pentacoordinate cytochrome c inhibits mitochondrial respiration.
Conclusions:
- Cytochrome c possesses a novel nitrite reductase activity, contributing to cellular NO signaling.
- This function is regulated by specific heme iron coordination and cellular conditions (anoxia, acidity).
- The findings suggest a new role for cytochrome c in regulating mitochondrial function and cellular signaling pathways, including hypoxic, redox, and apoptotic signaling.
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