Polarographic analyses of subsarcolemmal and intermyofibrillar mitochondria from rat skeletal and cardiac muscle

Manneschi, L.; Federico, Antonio

doi:10.1016/0022-510x(94)00227-f

Cited by 25 publications

(24 citation statements)

References 15 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Static morphological distinctions include mitochondria in intermyofibrillar locations, subsarcolemmal mito- chondria, and perinuclear mitochondria (16,17). It has also been suggested that these differentially localized mitochondria may have different functional properties (18,19).…”

Section: Discussionmentioning

confidence: 99%

Spatio-temporal oscillations of individual mitochondria in cardiac myocytes reveal modulation of synchronized mitochondrial clusters

Kurz

Aon

O’Rourke

et al. 2010

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

123

View full text Add to dashboard Cite

Mitochondrial networks in cardiac myocytes under oxidative stress show collective (cluster) behavior through synchronization of their inner membrane potentials (ΔΨ m ). However, it is unclear whether the oscillation frequency and coupling strength between individual mitochondria affect the size of the cluster and vice versa. We used the wavelet transform and developed advanced signal processing tools that allowed us to capture individual mitochondrial ΔΨ m oscillations in cardiac myocytes and examine their dynamic spatio-temporal properties. Heterogeneous frequency behavior prompted us to sort mitochondria according to their frequencies. Signal analysis of the mitochondrial network showed an inverse relationship between cluster size and cluster frequency as well as between cluster amplitude and cluster size. High cross-correlation coefficients between neighboring mitochondria clustered longitudinally along the myocyte striations, indicated anisotropic communication between mitochondria. Isochronal mapping of the onset of myocyte-wide ΔΨ m depolarization further exemplified heterogeneous ΔΨ m among mitochondria. Taken together, the results suggest that frequency and amplitude modulation of clusters of synchronized mitochondria arises by means of strong changes in local coupling between neighboring mitochondria.wavelets | frequency | amplitude | mitochondrial oscillator | mitochondrial coupling M itochondria in cardiac myocytes under the influence of substrate deprivation or oxidative stress have a fundamental role as determinants of cell life or death, with implications that scale to affect the function of the whole heart (1, 2). Cardiac mitochondria are organized in a highly ordered network consisting of intermyofibrillar, subcarcolemmal, and perinuclear (3) mitochondria whose coordinated function controls the energy metabolism of the myocyte (4).In cardiac myocytes, the localized perturbation of a few mitochondria within the overall mitochondrial network can trigger the transition from the physiological to the pathophysiological state by producing synchronized whole-myocyte oscillations of ΔΨ m that can be monitored with the fluorescent dye tetramethylrhodamine ethyl ester (TMRE) (5). The imbalance between reactive oxygen species (ROS) generation and ROS scavenging capacity in a significant proportion of the network (∼60%) (5) is thought to destabilize ΔΨ m beyond a critical point into a state of ROS-induced ROS release. Increased ROS overflow exceeding a threshold level results in the appearance of a spanning cluster of mitochondria oscillating in apparent synchrony throughout the cell as the mitochondrial network locks into a low-frequency, high-amplitude oscillatory mode (6, 7).In many disparate examples of physically and chemically coupled oscillators, synchronization of the system generally arises from an initial nucleus of (spontaneously) synchronized oscillators that integrate neighboring oscillators, thereby increasing the size and signal amplitude of the initial oscillatory nucleus (8-11).When the clus...

show abstract

Section: Discussionmentioning

confidence: 99%

Spatio-temporal oscillations of individual mitochondria in cardiac myocytes reveal modulation of synchronized mitochondrial clusters

Kurz

Aon

O’Rourke

et al. 2010

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

123

View full text Add to dashboard Cite

show abstract

“…In this study no attempt was made to differentially isolate subsarcolemmal (SSM) and intermyofibrillar mitochondrial populations, mitochondria with different morphology, organ localization, and biochemical characteristics (114,115); however, it is likely that our preparation was richer in SSM than intermyofibrillar due to the lack of protease use during the isolation procedure (which helps to improve the recovery of intermyofibrillar) and based on the rates of state 3 oxygen consumption rates (116,117). The electron transport chain activity of SSM has been found decreased in individuals with type 2 diabetes (118,119) to values similar to ours (2-3-fold lower state 3 oxygen uptake using NAD-and FAD-linked substrates).…”

Section: Ryr1 Mutation and Mitochondriamentioning

confidence: 99%

Basal Bioenergetic Abnormalities in Skeletal Muscle from Ryanodine Receptor Malignant Hyperthermia-susceptible R163C Knock-in Mice

Giulivi

Ross-Inta

Omanska-Klusek

et al. 2011

Journal of Biological Chemistry

View full text Add to dashboard Cite

Malignant hyperthermia (MH) and central core disease in humans have been associated with mutations in the skeletal ryanodine receptor (RyR1). Heterozygous mice expressing the human MH/central core disease RyR1 R163C mutation exhibit MH when exposed to halothane or heat stress. Considering that many MH symptoms resemble those that could ensue from a mitochondrial dysfunction (e.g. metabolic acidosis and hyperthermia) and that MH-susceptible mice or humans have a higher than normal cytoplasmic Ca 2؉ concentration at rest, we evaluated the role of mitochondria in skeletal muscle from R163C compared with wild type mice under basal (untriggered) conditions. R163C skeletal muscle exhibited a significant increase in matrix Ca 2؉ , increased reactive oxygen species production, lower expression of mitochondrial proteins, and higher mtDNA copy number. These changes, in conjunction with lower myoglobin and glycogen contents, Myh4 and GAPDH transcript levels, GAPDH activity, and lower glucose utilization suggested a switch to a compromised bioenergetic state characterized by both low oxidative phosphorylation and glycolysis. The shift in bioenergetic state was accompanied by a dysregulation of Ca 2؉ -responsive signaling pathways regulated by calcineurin and ERK1/2. Chronically elevated resting Ca 2؉ in R163C skeletal muscle elicited the maintenance of a fast-twitch fiber program and the development of insulin resistance-like phenotype as part of a metabolic adaptation to the R163C RyR1 mutation.

show abstract

“…These adaptations, which are thought to play a major role in mediating contraction-induced fiber type alterations, not only facilitate enhanced athletic performance but also contribute to improved whole body metabolic fitness. In contrast, deficiencies in mitochondrial oxidative capacity have been associated with the pathophysiology of aging (43) and metabolic diseases (26,28).Studies on mitochondrial function in skeletal or cardiac muscle present the added dimension of two distinct mitochondrial subpopulations that might exist as a continuous reticulum (25, 30) but differ according to their subcellular localization, morphology and biochemical properties (8,33,42). Subsarcolemmal (SS) mitochondria are located just underneath the sarcolemma and have a large, lamellar shape.…”

mentioning

confidence: 94%

“…Studies on mitochondrial function in skeletal or cardiac muscle present the added dimension of two distinct mitochondrial subpopulations that might exist as a continuous reticulum (25, 30) but differ according to their subcellular localization, morphology and biochemical properties (8,33,42). Subsarcolemmal (SS) mitochondria are located just underneath the sarcolemma and have a large, lamellar shape.…”

mentioning

confidence: 99%

Subsarcolemmal and intermyofibrillar mitochondria play distinct roles in regulating skeletal muscle fatty acid metabolism

Koves¹,

Noland²,

Bates³

et al. 2005

American Journal of Physiology-Cell Physiology

148

127

View full text Add to dashboard Cite

Skeletal muscle contains two populations of mitochondria that appear to be differentially affected by disease and exercise training. It remains unclear how these mitochondrial subpopulations contribute to fiber type-related and/or training-induced changes in fatty acid oxidation and regulation of carnitine palmitoyltransferase-1beta (CPT1beta), the enzyme that controls mitochondrial fatty acid uptake in skeletal muscle. To this end, we found that fatty acid oxidation rates were 8.9-fold higher in subsarcolemmal mitochondria (SS) and 5.3-fold higher in intermyofibrillar mitochondria (IMF) that were isolated from red gastrocnemius (RG) compared with white gastrocnemius (WG) muscle, respectively. Malonyl-CoA (10 muM), a potent inhibitor of CPT1beta, completely abolished fatty acid oxidation in SS and IMF mitochondria from WG, whereas oxidation rates in the corresponding fractions from RG were inhibited only 89% and 60%, respectively. Endurance training also elicited mitochondrial adaptations that resulted in enhanced fatty acid oxidation capacity. Ten weeks of treadmill running differentially increased palmitate oxidation rates 100% and 46% in SS and IMF mitochondria, respectively. In SS mitochondria, elevated fatty acid oxidation rates were accompanied by a 48% increase in citrate synthase activity but no change in CPT1 activity. Nonlinear regression analyses of mitochondrial fatty acid oxidation rates in the presence of 0-100 muM malonyl-CoA indicated that IC(50) values were neither dependent on mitochondrial subpopulation nor affected by exercise training. However, in IMF mitochondria, training reduced the Hill coefficient (P < 0.05), suggesting altered CPT1beta kinetics. These results demonstrate that endurance exercise provokes subpopulation-specific changes in mitochondrial function that are characterized by enhanced fatty acid oxidation and modified CPT1beta-malonyl-CoA dynamics.

show abstract

Polarographic analyses of subsarcolemmal and intermyofibrillar mitochondria from rat skeletal and cardiac muscle

Cited by 25 publications

References 15 publications

Spatio-temporal oscillations of individual mitochondria in cardiac myocytes reveal modulation of synchronized mitochondrial clusters

Spatio-temporal oscillations of individual mitochondria in cardiac myocytes reveal modulation of synchronized mitochondrial clusters

Basal Bioenergetic Abnormalities in Skeletal Muscle from Ryanodine Receptor Malignant Hyperthermia-susceptible R163C Knock-in Mice

Subsarcolemmal and intermyofibrillar mitochondria play distinct roles in regulating skeletal muscle fatty acid metabolism

Contact Info

Product

Resources

About