Remodeling pathway control of mitochondrial respiratory capacity by temperature in mouse heart: electron flow through the Q-junction in permeabilized fibers
Abstract Fuel substrate supply and oxidative phosphorylation are key determinants of muscle performance. Numerous studies of mammalian mitochondria are carried out (i) with substrate supply that limits electron flow, and (ii) far below physiological temperature. To analyze potentially implicated bia...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2017-06-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-017-02789-8 |
| _version_ | 1818856115266387968 |
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| author | Hélène Lemieux Pierre U. Blier Erich Gnaiger |
| author_facet | Hélène Lemieux Pierre U. Blier Erich Gnaiger |
| author_sort | Hélène Lemieux |
| collection | DOAJ |
| description | Abstract Fuel substrate supply and oxidative phosphorylation are key determinants of muscle performance. Numerous studies of mammalian mitochondria are carried out (i) with substrate supply that limits electron flow, and (ii) far below physiological temperature. To analyze potentially implicated biases, we studied mitochondrial respiratory control in permeabilized mouse myocardial fibers using high-resolution respirometry. The capacity of oxidative phosphorylation at 37 °C was nearly two-fold higher when fueled by physiological substrate combinations reconstituting tricarboxylic acid cycle function, compared with electron flow measured separately through NADH to Complex I or succinate to Complex II. The relative contribution of the NADH pathway to physiological respiratory capacity increased with a decrease in temperature from 37 to 25 °C. The apparent excess capacity of cytochrome c oxidase above physiological pathway capacity increased sharply under hypothermia due to limitation by NADH-linked dehydrogenases. This mechanism of mitochondrial respiratory control in the hypothermic mammalian heart is comparable to the pattern in ectotherm species, pointing towards NADH-linked mt-matrix dehydrogenases and the phosphorylation system rather than electron transfer complexes as the primary drivers of thermal sensitivity at low temperature. Delineating the link between stress and remodeling of oxidative phosphorylation is important for understanding metabolic perturbations in disease evolution and cardiac protection. |
| first_indexed | 2024-12-19T08:19:22Z |
| format | Article |
| id | doaj.art-59b9d2e8b934457799a51721c087f3f1 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-12-19T08:19:22Z |
| publishDate | 2017-06-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-59b9d2e8b934457799a51721c087f3f12022-12-21T20:29:25ZengNature PortfolioScientific Reports2045-23222017-06-017111310.1038/s41598-017-02789-8Remodeling pathway control of mitochondrial respiratory capacity by temperature in mouse heart: electron flow through the Q-junction in permeabilized fibersHélène Lemieux0Pierre U. Blier1Erich Gnaiger2D. Swarovski Research Laboratory, Department of Visceral, Transplant and Thoracic Surgery, Medical University InnsbruckLaboratoire de Physiologie Animale Intégrative, Université du QuébecD. Swarovski Research Laboratory, Department of Visceral, Transplant and Thoracic Surgery, Medical University InnsbruckAbstract Fuel substrate supply and oxidative phosphorylation are key determinants of muscle performance. Numerous studies of mammalian mitochondria are carried out (i) with substrate supply that limits electron flow, and (ii) far below physiological temperature. To analyze potentially implicated biases, we studied mitochondrial respiratory control in permeabilized mouse myocardial fibers using high-resolution respirometry. The capacity of oxidative phosphorylation at 37 °C was nearly two-fold higher when fueled by physiological substrate combinations reconstituting tricarboxylic acid cycle function, compared with electron flow measured separately through NADH to Complex I or succinate to Complex II. The relative contribution of the NADH pathway to physiological respiratory capacity increased with a decrease in temperature from 37 to 25 °C. The apparent excess capacity of cytochrome c oxidase above physiological pathway capacity increased sharply under hypothermia due to limitation by NADH-linked dehydrogenases. This mechanism of mitochondrial respiratory control in the hypothermic mammalian heart is comparable to the pattern in ectotherm species, pointing towards NADH-linked mt-matrix dehydrogenases and the phosphorylation system rather than electron transfer complexes as the primary drivers of thermal sensitivity at low temperature. Delineating the link between stress and remodeling of oxidative phosphorylation is important for understanding metabolic perturbations in disease evolution and cardiac protection.https://doi.org/10.1038/s41598-017-02789-8 |
| spellingShingle | Hélène Lemieux Pierre U. Blier Erich Gnaiger Remodeling pathway control of mitochondrial respiratory capacity by temperature in mouse heart: electron flow through the Q-junction in permeabilized fibers Scientific Reports |
| title | Remodeling pathway control of mitochondrial respiratory capacity by temperature in mouse heart: electron flow through the Q-junction in permeabilized fibers |
| title_full | Remodeling pathway control of mitochondrial respiratory capacity by temperature in mouse heart: electron flow through the Q-junction in permeabilized fibers |
| title_fullStr | Remodeling pathway control of mitochondrial respiratory capacity by temperature in mouse heart: electron flow through the Q-junction in permeabilized fibers |
| title_full_unstemmed | Remodeling pathway control of mitochondrial respiratory capacity by temperature in mouse heart: electron flow through the Q-junction in permeabilized fibers |
| title_short | Remodeling pathway control of mitochondrial respiratory capacity by temperature in mouse heart: electron flow through the Q-junction in permeabilized fibers |
| title_sort | remodeling pathway control of mitochondrial respiratory capacity by temperature in mouse heart electron flow through the q junction in permeabilized fibers |
| url | https://doi.org/10.1038/s41598-017-02789-8 |
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