Skeletal muscle sarcoplasmic reticulum contains a NADH-dependent oxidase  that generates superoxide

Xia, Ruohong; Webb, Jason A.; Gnall, Lisa L. M.; Cutler, Kerry; Abramson, Jonathan J.

doi:10.1152/ajpcell.00034.2002

Cited by 124 publications

(110 citation statements)

References 36 publications

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“…In line with our data, mitochondrial "contamination" has been observed in fractionated SR vesicles of skeletal muscle. Interestingly, those data showed 2.8-fold greater mitochondrial presence (verified by F 1 F 0 -ATPase quantitative Western blotting) in the heavy SR comprised predominantly of terminal cisternae than in the light SR fraction (19). Thus, the terminal cisternae, the SR subdomains where the bulk of the RyR reside (32,33), appeared to be preferred sites for SR-mitochondrial associations.…”

Section: Discussionmentioning

confidence: 90%

Physical Coupling Supports the Local Ca2+ Transfer between Sarcoplasmic Reticulum Subdomains and the Mitochondria in Heart Muscle

Garcı́a-Pérez

Hajnóczky

Csordás

2008

Journal of Biological Chemistry

135

112

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In many cell types, transfer of Ca 2؉ released via ryanodine receptors (RyR) to the mitochondrial matrix is locally supported by high [Ca 2؉ ] microdomains at close contacts between the sarcoplasmic reticulum (SR) and mitochondria. Here we studied whether the close contacts were secured via direct physical coupling in cardiac muscle using isolated rat heart mitochondria (RHMs). "Immuno-organelle chemistry" revealed RyR2 and calsequestrin-positive SR particles associated with mitochondria in both crude and Percoll-purified "heavy" mitochondrial fractions (cRHM and pRHM), to a smaller extent in the latter one. Mitochondria-associated vesicles were also visualized by electron microscopy in the RHMs. Western blot analysis detected greatly reduced presence of SR markers (calsequestrin, SERCA2a, and phospholamban) in pRHM, suggesting that the mitochondria-associated particles represented a small subfraction of the SR. signal propagation from the ryanodine receptors (RyR, the phylogenetic ancestors of the inositol 1,4,5-trisphosphate receptor) to the mitochondria in cardiac muscle cells (9, 10) and in skeletal muscle (11-13). However, whether the local Ca 2ϩ communication between the SR and mitochondria is supported by physical coupling is yet to be elucidated. Very recently, Protasi and co-workers (14, 15) have visualized tethering structures between SR and mitochondria in electron micrographs and tomographs of skeletal muscle, although those data did not examine the involvement of the tethers in the Ca 2ϩ communication between the organelles. A local metabolic triangle between the sarcomere, SR, and mitochondria that could be dissociated by limited proteolysis in permeabilized cardiomyocytes has also been described earlier (16). Here, we studied the preservation of the SR-mitochondrial associations and local Ca 2ϩ coupling between RyR and mitochondria by visualization of individual organelles and monitoring their function in mitochondria isolated from rat heart homogenates. MATERIALS AND METHODS Chemicals/ImmunochemicalsFluorescent probes and fluorescently labeled secondary antibodies were from Molecular Probes (Eugene, OR), except the Ca 2ϩ probes fura2 (K ϩ salt) and rhod2 acetoxymethylester (rhod2/AM), which were purchased from Teflabs (Austin, TX). Primary antibodies were obtained as follows: mouse monoclonal: anti-RyR2 from ABR (MA3-916), anti-phospholamban from Abcam (ab2865), and anti-cytochrome oxidase subunit 1 from Molecular Probes (A6403); rabbit polyclonal: anti-RyR2 * This work was supported by an American Heart Association Grant SDG 0435236N. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

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Section: Discussionmentioning

confidence: 90%

Physical Coupling Supports the Local Ca2+ Transfer between Sarcoplasmic Reticulum Subdomains and the Mitochondria in Heart Muscle

Garcı́a-Pérez

Hajnóczky

Csordás

2008

Journal of Biological Chemistry

135

112

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“…Reactive oxygen and nitrogen species generation by myofibres has been detected and quantified by a variety of methods including high‐performance liquid chromatography techniques,30, 51 electron‐spin resonance spectroscopy (also known as electron paramagnetic resonance),52, 53 fluorescence‐based microscopic assays,54, 55 spectrophotometry,56, 57 chemiluminescence58, 59 and transfection methods including in vivo 60, 61 and in vitro. 62 It is widely accepted that superoxide and nitric oxide (NO) are the primary radical species generated by skeletal muscle 46, 63.…”

Section: Skeletal Muscle Produces Reactive Oxygen and Nitrogen Speciesmentioning

confidence: 99%

Redox homeostasis and age‐related deficits in neuromuscular integrity and function

Sakellariou

Lightfoot

Earl

et al. 2017

J cachexia sarcopenia muscle

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Skeletal muscle is a major site of metabolic activity and is the most abundant tissue in the human body. Age‐related muscle atrophy (sarcopenia) and weakness, characterized by progressive loss of lean muscle mass and function, is a major contributor to morbidity and has a profound effect on the quality of life of older people. With a continuously growing older population (estimated 2 billion of people aged >60 by 2050), demand for medical and social care due to functional deficits, associated with neuromuscular ageing, will inevitably increase. Despite the importance of this ‘epidemic’ problem, the primary biochemical and molecular mechanisms underlying age‐related deficits in neuromuscular integrity and function have not been fully determined. Skeletal muscle generates reactive oxygen and nitrogen species (RONS) from a variety of subcellular sources, and age‐associated oxidative damage has been suggested to be a major factor contributing to the initiation and progression of muscle atrophy inherent with ageing. RONS can modulate a variety of intracellular signal transduction processes, and disruption of these events over time due to altered redox control has been proposed as an underlying mechanism of ageing. The role of oxidants in ageing has been extensively examined in different model organisms that have undergone genetic manipulations with inconsistent findings. Transgenic and knockout rodent studies have provided insight into the function of RONS regulatory systems in neuromuscular ageing. This review summarizes almost 30 years of research in the field of redox homeostasis and muscle ageing, providing a detailed discussion of the experimental approaches that have been undertaken in murine models to examine the role of redox regulation in age‐related muscle atrophy and weakness.

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“…A major point is that even low steady-state levels of assembled complex I may be sufficient to achieve enzymatic activities within the broad normal range. Furthermore, using rotenone-sensitive NADH oxidation as a measure for complex I may be critical especially for the low activity range, because a superoxide generating NADHdependent oxidase from skeletal muscle sarcoplasmatic reticulum, a common contaminant in mitochondrial preparations, was found recently to be highly sensitive to rotenone (23). In summary, in human skeletal muscle the entire portion of complex I is found to stably interact with complex III thereby forming functional respirasomes in the mitochondrial inner membrane.…”

Section: Figmentioning

confidence: 99%

Significance of Respirasomes for the Assembly/Stability of Human Respiratory Chain Complex I

Schägger

Coo

Bauer

et al. 2004

Journal of Biological Chemistry

291

221

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We showed that the human respiratory chain is organized in supramolecular assemblies of respiratory chain complexes, the respirasomes. The mitochondrial complexes I (NADH dehydrogenase) and III (cytochrome c reductase) form a stable core respirasome to which complex IV (cytochrome c oxidase) can also bind. An analysis of the state of respirasomes in patients with an isolated deficiency of single complexes provided evidence that the formation of respirasomes is essential for the assembly/stability of complex I, the major entry point of respiratory chain substrates. Genetic alterations leading to a loss of complex III prevented respirasome formation and led to the secondary loss of complex I. Therefore, primary complex III assembly deficiencies presented as combined complex III/I defects. This dependence of complex I assembly/stability on respirasome formation has important implications for the diagnosis of mitochondrial respiratory chain disorders.

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Skeletal muscle sarcoplasmic reticulum contains a NADH-dependent oxidase that generates superoxide

Cited by 124 publications

References 36 publications

Physical Coupling Supports the Local Ca2+ Transfer between Sarcoplasmic Reticulum Subdomains and the Mitochondria in Heart Muscle

Physical Coupling Supports the Local Ca2+ Transfer between Sarcoplasmic Reticulum Subdomains and the Mitochondria in Heart Muscle

Redox homeostasis and age‐related deficits in neuromuscular integrity and function

Significance of Respirasomes for the Assembly/Stability of Human Respiratory Chain Complex I

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