Regulation of mitochondrial respiration by inorganic phosphate; comparing permeabilized muscle fibers and isolated mitochondria prepared from type-1 and type-2 rat skeletal muscle

Scheibye‐Knudsen, Morten; Quistorff, Bjørn

doi:10.1007/s00421-008-0901-9

Cited by 41 publications

(24 citation statements)

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“…The baseline value of RCR in the present study was ϳ4, similar to previously reported values with permeabilized fibers in man and rat (8,51), albeit lower than what is usually found in isolated mitochondria from similar rat muscles (19). We found a pronounced increase (ϳ50%) in RCR after 6 mo of high-fat diet, and this increase showed a tendency to be higher in the groups that have also been exposed to maternal caloric restriction (Table 2).…”

Section: Postnatal High-fat Dietsupporting

confidence: 79%

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Changed mitochondrial function by pre- and/or postpartum diet alterations in sheep

Jørgensen

Gam

Andersen³

et al. 2009

American Journal of Physiology-Endocrinology and Metabolism

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In a sheep model, we investigated diet effects on skeletal muscle mitochondria to look for fetal programming. During pregnancy, ewes were fed normally (N) or were 50% food restricted (L) during the last trimester, and lambs born to these ewes received a normal (N) or a high-fat diet (H) for the first 6 mo of life. We examined mitochondrial function in permeabilized muscle fibers from the lambs at 6 mo of age (adolescence) and after 24 mo of age (adulthood). The postpartum H diet for the lambs induced an ϳ30% increase (P Ͻ 0.05) of mitochondrial V O2max and an ϳ50% increase (P Ͻ 0.05) of the respiratory coupling ratio (RCR) combined with lower levels of UCP3 and PGC-1␣ mRNA levels (P Ͻ 0.05). These effects proved to be reversible by a normal diet from 6 to 24 mo of age. However, at 24 mo, a long-term effect of the maternal gestational diet restriction (fetal programming) became evident as a lower V O2max (ϳ40%, P Ͻ 0.05), a lower state 4 respiration (ϳ40%, P Ͻ 0.05), and lower RCR (ϳ15%, P Ͻ 0.05). Both PGC-1␣ and UCP3 mRNA levels were increased (P Ͻ 0.05). Two analyzed muscles were affected differently, and muscle rich in type I fibers was more susceptible to fetal programming. We conclude that fetal programming, seen as a reduced V O2max in adulthood, results from gestational undernutrition. Postnatal high-fat diet results in a pronounced RCR and V O2max increase in adolescence. However, these effects are reversible by diet correction and are not maintained in adulthood. metabolic syndrome; high-fat diet; nutrient restriction; maternal diet; respiratory coupling ratio EPIDEMIOLOGICAL STUDIES IN HUMANS since the 1980s and subsequent clinical studies have revealed that small size or thinness at birth is associated with increased risk of developing metabolic dysfunctions like obesity, type 2 diabetes, and abnormal lipid and carbohydrate metabolism, leading to coronary heart disease and elevated blood pressure in adulthood (2, 21). This has spurred an increasing interest in the long-term consequences of maternal nutrition during pregnancy and early postnatal nutrition, a phenomenon first described by Hales and Barker (22) and termed metabolic programming. Although this concept is now widely accepted, the mechanisms behind it remain poorly understood. The observed effects reflect phenotypical alterations, probably established through epigenetic mechanisms, which occur as a result of fetal adaptations to intrauterine and probably early postnatal influences (23, 38). Maternal low-protein diet during pregnancy in rats may in adulthood result in reduced glucose tolerance and high blood pressure, evidently due to a prenatally programmed tendency to dysfunction of small arteries and abnormal pancreatic development (9, 17, 25). Likewise, maternal low-protein diets may result in very significantly shortened life span in mice offspring (44). Thus, both the type of malnutrition and the time of exposure during pregnancy appear to influence the programming effects observed later in life (21, 23). Furthermore, the potentially de...

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Section: Postnatal High-fat Dietsupporting

confidence: 79%

“…Mitochondrial function was tested in Oroboros Oxygraph-2K instruments (Oroboros, Innsbruck, Austria), operating six oxygraph chambers in parallel at 25°C (51). Approximately 2.5 mg of permeabilized fibers was added to 2 ml of medium in each chamber.…”

Section: Mitochondrial Functionmentioning

confidence: 99%

Changed mitochondrial function by pre- and/or postpartum diet alterations in sheep

Jørgensen

Gam

Andersen³

et al. 2009

American Journal of Physiology-Endocrinology and Metabolism

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“…Whether this occurs in skeletal muscle has yet to be established. These functional results combined with the proteomic data above and previous findings that the K m values for both ADP and P i are no different between mitochondria isolated from red and white muscle (36,44) suggest that many of the acute regulatory mechanisms within these mitochondria are also similarly poised when isolated from resting muscle. This similarity in protein content and activity level per mole enzyme, for those we queried, suggest that the configuration of mitochondria in these two muscle types is nearly identical to produce ATP as a function of mitochondrial volume.…”

Section: Discussionsupporting

confidence: 67%

Protein composition and function of red and white skeletal muscle mitochondria

Glancy

Balaban

2011

American Journal of Physiology-Cell Physiology

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Glancy B, Balaban RS. Protein composition and function of red and white skeletal muscle mitochondria. Am J Physiol Cell Physiol 300: C1280 -C1290, 2011. First published February 2, 2011 doi:10.1152/ajpcell.00496.2010.-Red and white muscles are faced with very different energetic demands. However, it is unclear whether relative mitochondrial protein expression is different between muscle types. Mitochondria from red and white porcine skeletal muscle were isolated with a Percoll gradient. Differences in protein composition were determined using blue native (BN)-PAGE, two-dimensional differential in gel electrophoresis (2D DIGE), optical spectroscopy, and isobaric tag for relative and absolute quantitation (iTRAQ). Complex IV and V activities were compared using BN-PAGE in-gel activity assays, and maximal mitochondrial respiration rates were assessed using pyruvate (P) ϩ malate (M), glutamate (G) ϩ M, and palmitoyl-carnitine (PC) ϩ M. Without the Percoll step, major cytosolic protein contamination was noted for white mitochondria. Upon removal of contamination, very few protein differences were observed between red and white mitochondria. BN-PAGE showed no differences in the subunit composition of Complexes I-V or the activities of Complexes IV and V. iTRAQ analysis detected 358 mitochondrial proteins, 69 statistically different. Physiological significance may be lower: at a 25% difference, 48 proteins were detected; at 50%, 14 proteins were detected; and 3 proteins were detected at a 100%. Thus any changes could be argued to be physiologically modest. One area of difference was fat metabolism where four ␤-oxidation enzymes were ϳ25% higher in red mitochondria. This was correlated with a 40% higher rate of PCϩM oxidation in red mitochondria compared with white mitochondria with no differences in PϩM and GϩM oxidation. These data suggest that metabolic demand differences between red and white muscle fibers are primarily matched by the number of mitochondria and not by significant alterations in the mitochondria themselves.proteomics; fast and slow-twitch muscle; iTRAQ; energetics; oxidative phosphorylation SKELETAL MUSCLE-specific oxygen consumption can increase over 100-fold from rest to maximal oxygen uptake (V O 2max ) (52). An additional threefold increase in power output can be achieved during maximal anaerobic exercise (43). Thus skeletal muscle is faced with a wide range of energetic demands dependent on both exercise intensity and duration. Slow and sustained activities such as maintaining posture or low-intensity exercise result in the recruitment of red, oxidative muscle fibers. Conversely, shorter bouts of high-intensity exercise are accomplished by the activation of white, glycolytic myocytes. Accordingly, protein expression in red and white fibers is tuned to meet their respective energetic demands. White muscle is characterized by a predominance of glycolytic enzymes and the fast isoforms of contractile proteins, whereas red muscle has greater abundance of contractile protein slow isoforms and higher ...

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“…Increased ADP and Pi, which are produced during ATP hydrolysis at muscle cross-bridges and other cellular processes like Ca 2ϩ pumping, are potent activators of mitochondrial respiration (19,37). In the current study, as isometric tension and ATP hydrolysis decline with reduced cross-bridge turnover and reduced Ca 2ϩ pumping during fatigue, this could explain the fall in respiration in FF fibers.…”

Section: Discussionmentioning

confidence: 72%

The O₂cost of the tension-time integral in isolated single myocytes during fatigue

Hepple

Howlett

Kindig

et al. 2010

American Journal of Physiology-Regulatory, Integrative and Comp

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One proposed explanation for the Vo(2) slow component is that lower-threshold motor units may fatigue and develop little or no tension but continue to use O(2), thereby resulting in a dissociation of cellular respiration from force generation. The present study used intact isolated single myocytes with differing fatigue resistance profiles to investigate the relationship between fatigue, tension development, and aerobic metabolism. Single Xenopus skeletal muscle myofibers were allocated to a fast-fatiguing (FF) or a slow-fatiguing (SF) group, based on the contraction frequency required to elicit a fall in tension to 60% of peak. Phosphorescence quenching of a porphyrin compound was used to determine Delta intracellular Po(2) (Pi(O(2)); a proxy for Vo(2)), and developed isometric tension was monitored to allow calculation of the time-integrated tension (TxT). Although peak DeltaPi(O(2)) was not different between groups (P = 0.36), peak tension was lower (P < 0.05) in SF vs. FF (1.97 +/- 0. 17 V vs. 2. 73 +/- 0.30 V, respectively) and time to 60% of peak tension was significantly longer in SF vs. FF (242 +/- 10 s vs. 203 +/- 10 s, respectively). Before fatigue, both DeltaPi(O(2)) and TxT rose proportionally with contraction frequency in SF and FF, resulting in DeltaPi(O(2))/TxT being identical between groups. At fatigue, TxT fell dramatically in both groups, but DeltaPi(O(2)) decreased proportionately only in the FF group, resulting in an increase in DeltaPi(O(2))/TxT in the SF group relative to the prefatigue condition. These data show that more fatigue-resistant fibers maintain aerobic metabolism as they fatigue, resulting in an increased O(2) cost of contractions that could contribute to the Vo(2) slow component seen in whole body exercise.

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Regulation of mitochondrial respiration by inorganic phosphate; comparing permeabilized muscle fibers and isolated mitochondria prepared from type-1 and type-2 rat skeletal muscle

Cited by 41 publications

References 50 publications

Changed mitochondrial function by pre- and/or postpartum diet alterations in sheep

Changed mitochondrial function by pre- and/or postpartum diet alterations in sheep

Protein composition and function of red and white skeletal muscle mitochondria

The O₂cost of the tension-time integral in isolated single myocytes during fatigue

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Regulation of mitochondrial respiration by inorganic phosphate; comparing permeabilized muscle fibers and isolated mitochondria prepared from type-1 and type-2 rat skeletal muscle

Cited by 41 publications

References 50 publications

Changed mitochondrial function by pre- and/or postpartum diet alterations in sheep

Changed mitochondrial function by pre- and/or postpartum diet alterations in sheep

Protein composition and function of red and white skeletal muscle mitochondria

The O2cost of the tension-time integral in isolated single myocytes during fatigue

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Product

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The O₂cost of the tension-time integral in isolated single myocytes during fatigue