Selective changes in mitochondria respiratory properties in oxidative or glycolytic muscle fibers isolated from G93AhumanSOD1 transgenic mice

Leclerc, Nathalie; Ribera, Florence; Zoll, Joffrey; Warter, Jean‐Marie; Poindron, Philippe; Lampert, Eliane; Borg, Jacques

doi:10.1016/s0960-8966(01)00240-1

Cited by 40 publications

(30 citation statements)

References 32 publications

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“…Outside the central nervous system, Mattiazzi et al [40] found basically the same defects in respiratory control ratio and ATP synthesis in mitochondria isolated from mutant SOD1 mouse liver. Our own fi ndings [17] and those reported by Leclerc et al [42] also showed a decreased respiratory control ratio in skeletal muscle mitochondria. In the same study, we also reported that the levels of ATP in muscle extracts from mutant SOD1 mice are decreased while those of uncoupling protein 3 are increased, therefore providing a putative mechanism of energy dissipation that could account for mitochondrial dysfunction in this tissue [17] .…”

Section: Mitochondria Are Functionally Abnormal In Als: Facts and Consupporting

confidence: 82%

Mitochondria in Amyotrophic Lateral Sclerosis: A Trigger and a Target

et al. 2004

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Strong evidence shows that mitochondrial dysfunction is involved in amyotrophic lateral sclerosis (ALS), but despite the fact that mitochondria play a central role in excitotoxicity, oxidative stress and apoptosis, the intimate underlying mechanism linking mitochondrial defects to motor neuron degeneration in ALS still remains elusive. Morphological and functional abnormalities occur in mitochondria in ALS patients and related animal models, although their exact nature and extent are controversial. Recent studies postulate that the mislocalization in mitochondria of mutant forms of copper-zinc superoxide dismutase (SOD1), the only well-documented cause of familial ALS, may account for the toxic gain of function of the enzyme, and hence induce motor neuron death. On the other hand, mitochondrial dysfunction in ALS does not seem to be restricted only to motor neurons as it is also present in other tissues, particularly the skeletal muscle. The presence of this ‘systemic’ defect in energy metabolism associated with the disease is supported in skeletal muscle tissue by impaired mitochondrial respiration and overexpression of uncoupling protein 3. In addition, the lifespan of transgenic mutant SOD1 mice is increased by a highly energetic diet compensating both the metabolic defect and the motorneuronal function. In this review, we will focus on the mitochondrial dysfunction linked to ALS and the cause-and-effect relationships between mitochondria and the pathological mechanisms thought to be involved in the disease.

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Section: Mitochondria Are Functionally Abnormal In Als: Facts and Consupporting

confidence: 82%

Mitochondria in Amyotrophic Lateral Sclerosis: A Trigger and a Target

et al. 2004

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“…In parallel, increased amounts of reactive oxygen species were found in mutant SOD1 muscle even before motor impairment (46). As a result, superoxide dismutase and catalase activities were shown to increase in an attempt to counterbalance the disturbances in the normal redox state of myofibers (65,72). The stimulation of these antioxidant defences, therefore, points to the presence of oxidative stress.…”

Section: Oxidative Stress and Mitochondrial Dysfunction Characterize mentioning

confidence: 99%

“…Whether or not these myofibers, or whole muscles, are affected by ALS in the same manner has been the subject of a number of (conflicting) studies. First experiments performed on mutant SOD1 mice showed decreased maximal oxygen consumption in mitochondria of oxidative slow-twitch soleus, compared to that observed in glycolytic fast-twitch extensor digitorum longus (EDL), suggesting that the disease would affect in particular muscles displaying oxidative metabolism (65). Mass spectrometry studies of the wobbler mouse model of motor neuron disease revealed an increase in the amount of the glycolytic enzyme G3PDH, hence suggesting a shift from oxidative to glycolytic metabolism during the course of the disease (110).…”

Section: Does Mutant Sod1 Toxicity Affect All Muscles Indistinctly?mentioning

confidence: 99%

The Role of Skeletal Muscle in Amyotrophic Lateral Sclerosis

et al. 2016

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Amyotrophic lateral sclerosis (ALS) is a fatal adult-onset disease primarily characterized by upper and lower motor neuron degeneration, muscle wasting and paralysis. It is increasingly accepted that the pathological process leading to ALS is the result of multiple disease mechanisms that operate within motor neurons and other cell types both inside and outside the central nervous system. The implication of skeletal muscle has been the subject of a number of studies conducted on patients and related animal models. In this review, we describe the features of ALS muscle pathology and discuss on the contribution of muscle to the pathological process. We also give an overview of the therapeutic strategies proposed to alleviate muscle pathology or to deliver curative agents to motor neurons. ALS muscle mainly suffers from oxidative stress, mitochondrial dysfunction and bioenergetic disturbances. However, the way by which the disease affects different types of myofibers depends on their contractile and metabolic features. Although the implication of muscle in nourishing the degenerative process is still debated, there is compelling evidence suggesting that it may play a critical role. Detailed understanding of the muscle pathology in ALS could, therefore, lead to the identification of new therapeutic targets.

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“…Mitochondrial dysfunction is not only restricted to the nervous system but is also present in other tissues, including liver (12), lymphocytes (13), and muscle (14). Wiedemann et al (15) found a deficiency of NADH:CoQ oxidoreductase in muscles of sporadic ALS.…”

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confidence: 99%

Evidence for defective energy homeostasis in amyotrophic lateral sclerosis: Benefit of a high-energy diet in a transgenic mouse model

Dupuis

Oudart

Frydman

et al. 2004

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

480

472

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Amyotrophic lateral sclerosis (ALS) is an adult-onset neurodegenerative disease characterized by selective loss of motor neurons and progressive muscle wasting. Growing evidence indicates that mitochondrial dysfunction, not only occurring in motor neurons but also in skeletal muscle, may play a crucial role in the pathogenesis. In this regard, the life expectancy of the ALS G93A mouse line is extended by creatine, an intracellular energy shuttle that ameliorates muscle function. Moreover, a population of patients with sporadic ALS exhibits a generalized hypermetabolic state of as yet unknown origin. Altogether, these findings led us to explore whether alterations in energy homeostasis may contribute to the disease process. Here, we show important variations in a number of metabolic indicators in transgenic ALS mice, which in all shows a metabolic deficit. These alterations were accompanied early in the asymptomatic phase of the disease by reduced adipose tissue accumulation, increased energy expenditure, and concomitant skeletal muscle hypermetabolism. Compensating this energetic imbalance with a highly energetic diet extended mean survival by 20%. In conclusion, we suggest that hypermetabolism, mainly of muscular origin, may represent by itself an additional driven force involved in increasing motor neuron vulnerability.

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Selective changes in mitochondria respiratory properties in oxidative or glycolytic muscle fibers isolated from G93AhumanSOD1 transgenic mice

Cited by 40 publications

References 32 publications

Mitochondria in Amyotrophic Lateral Sclerosis: A Trigger and a Target

Mitochondria in Amyotrophic Lateral Sclerosis: A Trigger and a Target

The Role of Skeletal Muscle in Amyotrophic Lateral Sclerosis

Evidence for defective energy homeostasis in amyotrophic lateral sclerosis: Benefit of a high-energy diet in a transgenic mouse model

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