Cytochrome redox states and respiratory control in mouse and beef heart mitochondria at steady-state levels of hypoxia.

Abstract

Mitochondrial control of cellular redox states is a fundamental component of cell signaling in the coordination of core energy metabolism and homeostasis during normoxia and hypoxia. We investigated the relationship between cytochrome redox states and mitochondrial oxygen consumption at steady-state levels of hypoxia in mitochondria isolated from beef and mouse heart (BHImt, MHImt), comparing two species with different cardiac dynamics and local oxygen demands. A low-noise, rapid spectrophotometric system using visible light for the measurement of cytochrome redox states was combined with high-resolution respirometry. Monophasic hyperbolic relationships were observed between oxygen consumption, JO2, and oxygen partial pressure, Po2, within the range <1.1 kPa (8.3 mmHg; 13 μM). P50j (Po2 at 0.5·Jmax) was 0.015 ± 0.0004 and 0.021 ± 0.003 kPa (0.11 and 0.16 mmHg) for BHImt and MHImt, respectively. Maximum oxygen consumption, Jmax, was measured at saturating ADP levels (OXPHOS capacity) with Complex I-linked substrate supply. Redox states of cytochromes aa3 and c were biphasic hyperbolic functions of Po2. The relationship between cytochrome oxidation state and oxygen consumption revealed a separation of distinct phases from mild to severe and deep hypoxia. When cytochrome c oxidation increased from fully reduced to 45% oxidized at 0.1 Jmax, Po2 was as low as 0.002 kPa (0.02 μM), and trace amounts of oxygen are sufficient to partially oxidize the cytochromes. At higher Po2 under severe hypoxia, respiration increases steeply, whereas redox changes are small. Under mild hypoxia, the steep slope of oxidation of cytochrome c when flux remains more stable represents a cushioning mechanism that helps to maintain respiration high at the onset of hypoxia.

• Authors: David K Harrison, Mario Fasching, Mona Fontana-Ayoub, Erich Gnaiger
• Journal: Journal of applied physiology (Bethesda, Md. : 1985) (J Appl Physiol (1985)) Vol. 119 Issue 10 Pg. 1210-8 (Nov 15 2015) ISSN: 1522-1601 [Electronic] United States
• PMID: 26251509 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 the American Physiological Society.

Chemical References

• Cytochromes

Topics

• Animals
• Cattle
• Cell Hypoxia (physiology)
• Cell Respiration (physiology)
• Cytochromes (metabolism)
• Male
• Mice
• Mice, Inbred C57BL
• Mitochondria, Heart (metabolism)
• Oxidation-Reduction
• Oxygen Consumption (physiology)