Difference between revisions of "Hempenstall 2012 Mech Ageing Dev"
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|year=2012 | |year=2012 | ||
|journal=Mech Ageing Dev | |journal=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. | |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 | |keywords=Dietary restriction | ||
|mipnetlab=UK Aberdeen Selman C | |mipnetlab=UK Aberdeen Selman C | ||
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|topics=Mitochondrial Biogenesis; Mitochondrial Density | |topics=Mitochondrial Biogenesis; Mitochondrial Density | ||
}} | }} | ||
== Comment: Resting | == 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 | 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 ETS capacity should be corrected for ROX. --[[User:Gnaiger Erich|Gnaiger Erich]] 19:51, 7 March 2012 (CET) | ||
* Further information: [[Glossary: Respiratory states]] | |||
Revision as of 20:51, 7 March 2012
| 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. |
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:
Stress:Aging; Senescence"Aging; Senescence" is not in the list (Cell death, Cryopreservation, Ischemia-reperfusion, Permeability transition, Oxidative stress;RONS, Temperature, Hypoxia, Mitochondrial disease) of allowed values for the "Stress" property. Organism: Mouse Tissue;cell: Skeletal Muscle"Skeletal Muscle" is not in the list (Heart, Skeletal muscle, Nervous system, Liver, Kidney, Lung;gill, Islet cell;pancreas;thymus, Endothelial;epithelial;mesothelial cell, Blood cells, Fat, ...) of allowed values for the "Tissue and cell" property. Preparation: Permeabilized Tissue"Permeabilized Tissue" is not in the list (Intact organism, Intact organ, Permeabilized cells, Permeabilized tissue, Homogenate, Isolated mitochondria, SMP, Chloroplasts, Enzyme, Oxidase;biochemical oxidation, ...) of allowed values for the "Preparation" property. Enzyme: Marker Enzyme"Marker Enzyme" is not in the list (Adenine nucleotide translocase, Complex I, Complex II;succinate dehydrogenase, Complex III, Complex IV;cytochrome c oxidase, Complex V;ATP synthase, Inner mt-membrane transporter, Marker enzyme, Supercomplex, TCA cycle and matrix dehydrogenases, ...) of allowed values for the "Enzyme" property. Regulation: Mitochondrial Biogenesis; Mitochondrial Density"Mitochondrial Biogenesis; Mitochondrial Density" is not in the list (Aerobic glycolysis, ADP, ATP, ATP production, AMP, Calcium, Coupling efficiency;uncoupling, Cyt c, Flux control, Inhibitor, ...) of allowed values for the "Respiration and regulation" property.
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 ETS capacity should be corrected for ROX. --Gnaiger Erich 19:51, 7 March 2012 (CET)
- Further information: Glossary: Respiratory states
