Lemieux 2017 bioRxiv
|Lemieux H, Blier PU, Gnaiger E (2017) Remodeling pathway control of oxidative phosphorylation by temperature in the heart. bioRxiv doi: https://doi.org/10.1101/103457.|
Abstract: The capacity of mitochondrial oxidative phosphorylation (OXPHOS) and fuel substrate supply are key determinants of cardiac muscle performance. Although temperature exerts a strong effect on energy metabolism, until recently numerous respiratory studies of mammalian mitochondria have been carried out below physiological temperature, with substrates supporting submaximal respiratory capacity. We measured mitochondrial respiration as a function of temperature in permeabilized fibers from the left ventricle of the mouse heart. At 37 °C, OXPHOS capacity with electron entry through either Complex I or Complex II into the Q-junction was about half of respiratory capacity with the corresponding physiological substrate combination reconstituting tricarboxylic acid cycle function with convergent electron flow through the NADH&succinate-pathway. When separating the component core mitochondrial pathways, the relative contribution of the NADH-pathway increased with a decrease of temperature from 37 to 25 ºC. The additive effect of convergent electron flow has profound consequences for optimization of mitochondrial respiratory control. The apparent excess capacity of cytochrome c oxidase was 0.7 above convergent NADH&succinate-pathway capacity, but would be overestimated nearly 2-fold with respect to respiration restricted by provision of NADH-linked substrates only. The apparent excess capacity of cytochrome c oxidase increased sharply at 4 °C, caused by a strong temperature dependence of and OXPHOS 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 and likely modulators of temperature adaptation and acclimatization. Delineating the link between stress and remodeling of OXPHOS is critically important for improving our understanding of metabolic perturbations in disease evolution and cardiac protection. Temperature is not a trivial experimental parameter to consider when addressing these questions.
Labels: MiParea: Respiration, Comparative MiP;environmental MiP
Organism: Mouse Tissue;cell: Heart Preparation: Permeabilized tissue Enzyme: Marker enzyme Regulation: Temperature, Threshold;excess capacity, Uncoupler Coupling state: LEAK, OXPHOS, ETS Pathway: N, S, NS HRR: Oxygraph-2k
Additional: SUIT_NS(PGM)02, SUIT_NS(PGM)03, MitoFitPublication
- Dear colleague,
- This is a »link to a manuscript in which we implemented the ‘new terminology’ on SUIT protocols and coupling/pathway control states. The terminology was presented and discussed at the Verona Core Group /WG1 meeting. The complete manuscript is uploaded on the Preprint server bioXriv, where it is publicly available to the scientific community, and is open for discussion and for posting corresponding comments on the bioXriv server.
- I expect that not all MITOEAGLE members will agree on the ‘new terminology’, in which case I would welcome your critical comments, which can be posted on the bioXriv server. This will provide a good speed for:
- further discussions at the Barcelona WG1 meeting;
- preparing our MITOEAGLE review on terminology, which then can also be uploaded on bioXriv prior to publication in a journal.
- Below are further links.
- Best regards,
- NADH-linked or N-pathways (CI-entry into Q); succinate-linked or S-pathway (CII-entry into Q); NS-pathway (convergent CI&II-entry into Q)
- MitoPedia: SUIT
Nomenclature and further references
- Li P, Wang B, Sun F, Li Y, Li Q, Lang H, Zhao Z, Gao P, Zhao Y, Shang Q, Liu D, Zhu Z (2015) Mitochondrial respiratory dysfunctions of blood mononuclear cells link with cardiac disturbance in patients with early-stage heart failure. Sci Rep 5:10229. - »Bioblast link«
- Lemieux H, Garedew A, Blier PU, Tardif J-C, Gnaiger E (2006) Temperature effects on the control and capacity of mitochondrial respiration in permeabilized fibers of the mouse heart. Biochim Biophys Acta, EBEC Short Reports Suppl 14 (2006):201-2. - »Bioblast link«
- Garedew A, Lemieux H, Schachner T, Blier PU, Tardif J-C, Gnaiger E (2006) High excess capacity of cytochrome c oxidase in permeabilized fibers of the mouse heart. Biochim Biophys Acta, EBEC Short Reports Suppl 14 (2006):167-8. - »Bioblast link«
Preprints for Gentle Science
In the spirit of COST Action MITOEAGLE WG1
Contribution to MitoFit