Lemieux 2017 bioRxiv 103457

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.

» Preprint Open Access

Lemieux H, Blier PU, Gnaiger E (2017) bioRxiv

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.

• Bioblast editor: Gnaiger E • O2k-Network Lab: CA_Edmonton_Lemieux H, CA_Rimouski_Blier PU, AT_Innsbruck_OROBOROS, AT_Innsbruck_Gnaiger E

Labels: MiParea: Respiration, Comparative MiP;environmental MiP 

Organism: Mouse  Tissue;cell: Heart  Preparation: Permeabilized tissue  Enzyme: Marker enzyme  Regulation: Temperature  Coupling state: LEAK, OXPHOS, ETS"ETS" is not in the list (LEAK, ROUTINE, OXPHOS, ET) of allowed values for the "Coupling states" property.  Pathway: N, S, NS  HRR: Oxygraph-2k 

SUIT NS(PGM)02, SUIT NS(PGM)03 

SUIT protocols

• SUIT 1: SUIT NS(PGM)02
• SUIT 2: SUIT NS(PGM)03

Nomenclature

• MitoPedia: Respiratory states / MITOEAGLE: Respiratory states
• MitoPedia: Respiratory control ratios
• MitoPedia: SUIT

Abstracts

• 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«