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Hempenstall 2012 Mech Ageing Dev

From Bioblast
Publications in the MiPMap
Hempenstall S, Page MM, Wallen KR, Selman C (2012) Dietary restriction increases skeletal muscle mitochondrial respiration but not mitochondrial content in C57BL/6 mice. Mech Ageing Dev 133:37-45.

» PMID:22212415

Hempenstall S, Page MM, Wallen KR, Selman C (2012) Mech Ageing Dev

Abstract: Dietary restriction (DR) is suggested to induce mitochondrial biogenesis, although recently this has been challenged. Here we determined the impact of 1, 9 and 18 months of 30% DR in male C57BL/6 mice on key mitochondrial factors and on mitochondrial function in skeletal muscle, relative to age-matched ad libitum (AL) controls. We examined proteins and mRNAs associated with mitochondrial biogenesis and measured mitochondrial respiration in permeabilised myofibres using high-resolution respirometry. 30% DR, irrespective of duration, had no effect on citrate synthase activity. In contrast, total and nuclear protein levels of PGC-1α, mRNA levels of several mitochondrial associated proteins (PGC-1α, Nrf1, Core 1, Cox IV, Atps) and cytochrome c oxidase content were increased in skeletal muscle of DR mice. Furthermore, a range of mitochondrial respiration rates were increased significantly by DR, with DR partially attenuating the age-related decline in respiration observed in AL controls. Therefore, DR did not increase mitochondrial content, as determined by citrate synthase, in mouse skeletal muscle. However, it did induce a PGC-1α adaptive response and increased mitochondrial respiration. Thus, we suggest that a functionally 'efficient' mitochondrial electron transport chain may be a critical mechanism underlying DR, rather than any net increase in mitochondrial content per se. Supplementary data associated with this article can be found, in the online version, at doi:10.1016/j.mad.2011.12.002. Keywords: Dietary restriction

O2k-Network Lab: UK Aberdeen Selman C

Labels: MiParea: Respiration, mt-Biogenesis;mt-density, Exercise physiology;nutrition;life style  Pathology: Aging;senescence 

Organism: Mouse  Tissue;cell: Skeletal muscle  Preparation: Permeabilized tissue  Enzyme: Marker enzyme 

HRR: Oxygraph-2k 

Comment: Resting state

The respirometric protocol started with permeabilized fibres added to mitochondrial respiration medium (with inorganic phosphate) in the absence of carbon-substrates and without ADP or ATP. The authors refer to this as 'Resting state (A; without any substrate addition)' (Fig. 4A). In physiology, however, a 'starvation state' is strictly distinguished from metabolism in a 'resting state'. Mitochondria in the absence of added carbon-substrates are starved, gradually exhausting the endogenous substrates remaining in the mitochondria after tissue permeabilization. When the key enzymes of the electron transport system are either inhibited or fully deprived of substrate, then residual oxygen consumption (ROX) is observed, distinct from resting respiration. The term 'resting respiration', therefore, is frequently used synonymous with LEAK respiration (L), which is measured after addition of carbon-substrates either in the absence of ADP (Fig. 4B) or after inhibition of the phosphorylation system (oligomycin, atractyloside, etc.). If ROX is measured carefully (i.e. a stimulatory effect of residual endogenous substrates must be excluded), then mitochondrial LEAK, OXPHOS and ET capacity should be corrected for ROX. The basic respiratory patterns in Fig. 4 become more clear with an emphasis on the fact that Fig. 4A carries information very different from the other panels.--Gnaiger Erich 19:51, 7 March 2012 (CET)