Chemical energetics of slow- and fast-twitch muscles of the mouse.

Crow, Michael T.; Kushmerick, Martin J.

doi:10.1085/jgp.79.1.147

Cited by 498 publications

(399 citation statements)

References 26 publications

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“…Eliminating oxidative phosphorylation by anoxia permitted the use of PCr breakdown to measure the net cell ATP turnover that the mitochondria meets under resting, oxygenated conditions. Validation of this approach comes from a direct comparison of mitochondrial respiration under aerobic conditions vs. net ATP turnover during anoxia in isolated mouse muscles (27) and in vivo in rattlesnake tailshaker muscle (28). Anoxia of up to 30 min in intact muscle does not impact the activity of a key ATPase in resting muscle, Na-K-ATPase (29), and our measurements of glycolysis indicate a negligible contribution to ATP supply during the anoxic period (Ͻ8%).…”

Section: Discussionmentioning

confidence: 82%

“…In contrast, activation of the myosin ATPases results in large differences in ATP turnover between muscle fiber types during exercise. Mouse muscles representing the extremes of fiber type composition, showed the same energetic fluxes at rest but greater than the 2-fold differences in flux during exercise at the same stimulation rate (27). Thus, eliminating contractile energetic differences by studying resting muscle reveals little difference in ATP turnover but does reveal a significant difference in mitochondrial O 2 uptake between muscles of the same subject.…”

Section: Discussionmentioning

confidence: 89%

See 1 more Smart Citation

Mild mitochondrial uncoupling impacts cellular aging in human muscles in vivo

Amara¹,

Shankland²,

Jubrias³

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

202

195

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Faster aging is predicted in more active tissues and animals because of greater reactive oxygen species generation. Yet age-related cell loss is greater in less active cell types, such as type II muscle fibers. Mitochondrial uncoupling has been proposed as a mechanism that reduces reactive oxygen species production and could account for this paradox between longevity and activity. We distinguished these hypotheses by using innovative optical and magnetic resonance spectroscopic methods applied to noninvasively measured ATP synthesis and O 2 uptake in vivo in human muscle. Here we show that mitochondrial function is unchanged with age in mildly uncoupled tibialis anterior muscle (75% type I) despite a high respiratory rate in adults. In contrast, substantial uncoupling and loss of cellular [ATP] indicative of mitochondrial dysfunction with age was found in the lower respiring and well coupled first dorsal interosseus (43-50% type II) of the same subjects. These results reject respiration rate as the sole factor impacting the tempo of cellular aging. Instead, they support mild uncoupling as a mechanism protecting mitochondrial function and contributing to the paradoxical longevity of the most active muscle fibers. magnetic resonance spectroscopy ͉ optical spectroscopy ͉ oxidative phosphorylation T he rate-of-living hypothesis proposes that higher rates of oxidative metabolism cause an increased production of reactive oxygen species (ROS) (1), leading to oxidative damage and mitochondrial dysfunction with age. However, mice with the lowest resting respiration rate have been shown to have the shortest longevity (2). Similarly, isolated muscle fibers show greater generation of ROS in type II fibers (3), which have the lowest oxidative capacity and chronic activity levels. This fiber type also has the shortest longevity and is the first to be lost with age (4). Thus, the tempo of aging appears to vary among mice and muscle fiber types but in an opposite manner than predicted by the rate-of-living hypothesis, with the least active having the shortest longevity.A physiological mechanism that could account for this paradox is mild mitochondrial uncoupling, which has been proposed to ameliorate ROS production by reducing reverse electron flow and superoxide generation (5). Consistent with this prediction are findings in mice with high respiration rates that showed elevated proton leak in isolated muscle mitochondria as a result of activation of the adenine nucleotide translocator and uncoupling protein 3. Mild uncoupling resulting from activation of these mitochondrial factors in type I muscle fibers could reduce ROS production, protect mitochondria from damage, and account for the longevity of this fiber type with age. A number of studies have provided evidence of mild uncoupling in human muscles (6, 7) but have not tested whether this uncoupling protects against mitochondrial dysfunction and cellular aging.New methods permit measurement of mitochondrial coupling in vivo by using a combination of noninvasive spectroscopi...

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Section: Discussionmentioning

confidence: 82%

Section: Discussionmentioning

confidence: 89%

Mild mitochondrial uncoupling impacts cellular aging in human muscles in vivo

Amara¹,

Shankland²,

Jubrias³

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

202

195

View full text Add to dashboard Cite

show abstract

“…On the other hand all fibres may be recruited at the start of exercise, however there may be a progressive increase over time in the neural stimulation of the type II fibres. As type II muscle fibres are less efficient than type I muscle fibres and posses an 18% lower phosphate produced to oxygen consumed ratio (P:O 2 ratio), 33,34 recruitment of these fibres would result in more oxygen consumption when required to maintain a given work rate. No correlation existed between the magnitude of the relative SC and the percentage of type IIx muscle fibres for the either the Tr or the RA groups, or when both groups were combined.…”

Section: Slow Component Of V á O 2 Kineticsmentioning

confidence: 99%

Slow component of V̇O2 kinetics: the effect of training status, fibre type, UCP3 mRNA and citrate synthase activity

et al. 2002

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OBJECTIVE:In healthy individuals performing constant-load exercise at intensities above the lactate threshold a secondary rise in pulmonary oxygen uptake (V O 2 ) occurs. V O 2 reaches a maximum and exhaustion rapidly prevails for a range of work rates lower than the maximal work rate achieved during a conventional rapid-incremental test. This phenomenon is called the slow component (SC) of V O 2 kinetics and represents an increase in V O 2 without an increase in work rate. Although still under debate, the magnitude of the SC is believed to be associated with the percentage of type II muscle fibres and their recruitment. In this study we investigated the relationship between the magnitude of the relative SC, citrate synthase activity, UCP2 and UCP3 mRNA levels and muscle fibre composition in both endurance-trained and recreationally active subjects. METHOD: The magnitude of the relative SC was measured in 12 endurance-trained (Tr) and 15 recreationally active (RA) male subjects. The magnitude of the relative SC was determined as the difference between the end-exercise V O 2 and 3 min V O 2 divided by the difference between end-exercise V O 2 and baseline V O 2 . UCP2 and UCP3 mRNA expression in the vastus lateralis was measured by RT-PCR with b-actin mRNA used as an internal control. These values were also normalized against cytochromeb mRNA to control for training induced changes in mitochondria when comparing the Tr and RA groups. Type I, IIa and IIx skeletal muscle fibre composition was determined using a routine myosin ATPase histochemical staining technique. Citrate synthase (CS) activity was measured using spectrophotometric detection. RESULTS:The magnitude of the relative SC of the Tr group had the highest correlation with citrate synthase activity (r ¼ 7 0.90, P < 0.001) and that of the RA group with V O 2 peak (r ¼ 7 0.68, P < 0.01). For the Tr group other correlations with the magnitude of the relative SC included UCP3 mRNA levels (r ¼ 0.69, P < 0.05) and the percentage of type I fibres (r ¼ 7 0.58, P < 0.05), while for the RA group they included UCP3 mRNA (r ¼ 0.58, P < 0.05) and the percentage of type IIa muscle fibres (r ¼ 0.59, P < 0.05). The Tr subjects had a lower relative SC (P ¼ 0.04) and a lower expression of UCP2 (P ¼ 0.04), and UCP3 mRNA (P ¼ 0.01) than the RA subjects. When the groups were combined the magnitude of the relative SC correlated with UCP3 mRNA (r ¼ 0.70, P < 0.01), percentage of type IIa muscle fibres (r ¼ 0.60, P < 0.01) and V O 2 peak (r ¼ 7 0.73, P < 0.01). Additionally UCP3 mRNA correlated with the percentage of type IIa muscle fibres (r ¼ 0.63, P < 0.001). CONCLUSION: Citrate synthase activity and V O 2 peak are indicators of aerobic fitness. The high negative correlations between the magnitude of the relative SC and citrate synthase activity and V O 2 peak, of the Tr and RA subjects, respectively, suggests that the magnitude of the relative SC is inversely correlated with aerobic fitness. Additionally the correlations between UCP3 mRNA and the magnitude of the relative SC...

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“…Type 11 have a lower oxidative efficiency than type I muscle fibers, with the P:O ratio found to be 18% lower in the former (47,48). It has been observed that UCP3 protein content is expressed decrescendo in Ilx>lla>1 muscle fiber types in both healthy and diabetic subjects (49) as weil as in endurance trained cyclists.…”

Section: Regulation Of Energy Expenditurementioning

confidence: 99%

Old and new determinants in the regulation of energy expenditure

Russell¹,

Giacobino²

2002

J Endocrinol Invest

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ABSTRACT. Bw gain is controlled by energy intake on one hand and expenditure on the other. The components of energy expenditure are basal metabolism, exercise induced thermogenesis and adaptive UNCOUPLING PROTE/N-1 (UCP1)In rodents, brown adipose tissue (BAT) is an important site of adaptive thermogenesis. Cold exposure has for long been known to induce, via stimulation of the sympathetic nervous system, an increase in BAT thermogenesis referred to as adaptive cold-induced thermogenesis (CIT), (1). Furthermore, it has been observed that voluntary overeating induced in rats by the administration of a palatable, so-called "cafeteria" diet also induced an increase in BAT thermogenesis which was called adaptive diet-induced thermogenesis (OIT) (2).The main producer of heat in BAT is the uncoupling protein-1 (UCP1). This mitochondria inner membrane protein uncouples oxidative phosphorylation by dissipating the proton gradient generated by the re-oxidation of NAOH H+ in the respiratory chain. The UCP1-mediated proton transport requires the presence of fatty acids and is specificalIy inhibited by purine di-and triphosphate nucleotides (3). The consequence of UCP1 activity is a decrease in the amount of ATP formed by the ATP synthase and energy dissipation as heat. UCP1 knockout mice were generated and they were unable to maintain their body temperature upon cold exposure but did not become obese (4).These data confirmed the importance of UCP1 in Key-words: ßTadrenoceptor. uncoupling CIT and suggested that, in UCP1 knockout mice, alternative mechanisms for maintaining body mass wh ich could not protect against the cold were turned on, In humans, BAT is present in newborn babies and decreases in 4-6 months after birth (5, 6). It is therefore generally believed that there is no UCP1 in human adults. THE ßTADRENOCEPTOR -UCP1 AX/SThe family of the ß-adrenoceptors were considered to consist of ß1-and ß-rsubtypes until1989 when a third subtype was cloned (7). This third subtype called the ß3-adrenoceptor was found to be the predominant ß-subtype in rodent BAT and white adipose tissue (WAT) (8,9). When the BAT sympathetic nervous system activity is increased by cold exposure or overfeeding, the stimulatory effect on UCP1 activity and expression is therefore mediated essentially by the ß3-adrenoceptor (9). Therefore, the ß3-adrenoceptor-UCP1-axis is a major determinant of rodent adaptive thermogenesis, The ß3-adrenoceptor was found to be down-regulated in obese fa/fa Zucker rat BAT and WAT (8) and in obese ob/ob mouse adipose tissues compa red to lean animals (10). In ß3-adrenoceptor knockout mice, the capacity to adapt to a cold environment was fully preserved, but there was an increase in fat deposition under basal conditions and in response to a high fat diet (11). These data confirmed the importance of the ß3-adrenoceptor in OIT and suggested that, in the ß3-adrenoceptor knockout mice, alternative mechanisms for maintaining body temperature were turned on. In rodents, cold exposure was found to recruit mul- A.P. Russe 1...

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Chemical energetics of slow- and fast-twitch muscles of the mouse.

Cited by 498 publications

References 26 publications

Mild mitochondrial uncoupling impacts cellular aging in human muscles in vivo

Mild mitochondrial uncoupling impacts cellular aging in human muscles in vivo

Slow component of V̇O2 kinetics: the effect of training status, fibre type, UCP3 mRNA and citrate synthase activity

Old and new determinants in the regulation of energy expenditure

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