Mitochondrial breakdown in skeletal muscle and the emerging role of the lysosomes

Triolo, Matthew; Hood, David A.

doi:10.1016/j.abb.2018.11.004

Cited by 31 publications

(32 citation statements)

References 92 publications

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“…More recently, UNC-51-like kinase 1 (ULK1)-mediated phosphorylation of Beclin1 was also shown to facilitate translocation of Parkin to the outer mitochondrial membrane [39]. Parkin can poly-ubiquitinate proteins on the outer mitochondrial membrane [40], which leads to binding of adaptor proteins such as P62 that can, in turn, bind microtubule-associated protein 1A/1B-lightchain 3 (LC3)-II, leading to mitophagy [38,41]. Consequently, our results may indicate impaired capacity for initiation of PINK1-Parkin-mediated mitophagy and, hence, dysregulation of mitochondrial quality control.…”

Section: Discussionmentioning

confidence: 99%

Mitochondrial Structure and Function in the Metabolic Myopathy Accompanying Patients with Critical Limb Ischemia

Groennebaek

Billeskov

Schytz

et al. 2020

Cells

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Mitochondrial dysfunction has been implicated as a central mechanism in the metabolic myopathy accompanying critical limb ischemia (CLI). However, whether mitochondrial dysfunction is directly related to lower extremity ischemia and the structural and molecular mechanisms underpinning mitochondrial dysfunction in CLI patients is not understood. Here, we aimed to study whether mitochondrial dysfunction is a distinctive characteristic of CLI myopathy by assessing mitochondrial respiration in gastrocnemius muscle from 14 CLI patients (65.3 ± 7.8 y) and 15 matched control patients (CON) with a similar comorbidity risk profile and medication regimen but without peripheral ischemia (67.4 ± 7.4 y). Furthermore, we studied potential structural and molecular mechanisms of mitochondrial dysfunction by measuring total, sub-population, and fiber-type-specific mitochondrial volumetric content and cristae density with transmission electron microscopy and by assessing mitophagy and fission/fusion-related protein expression. Finally, we asked whether commonly used biomarkers of mitochondrial content are valid in patients with cardiovascular disease. CLI patients exhibited inferior mitochondrial respiration compared to CON. This respiratory deficit was not related to lower whole-muscle mitochondrial content or cristae density. However, stratification for fiber types revealed ultrastructural mitochondrial alterations in CLI patients compared to CON. CLI patients exhibited an altered expression of mitophagy-related proteins but not fission/fusion-related proteins compared to CON. Citrate synthase, cytochrome c oxidase subunit IV (COXIV), and 3-hydroxyacyl-CoA dehydrogenase (β-HAD) could not predict mitochondrial content. Mitochondrial dysfunction is a distinctive characteristic of CLI myopathy and is not related to altered organelle content or cristae density. Our results link this intrinsic mitochondrial deficit to dysregulation of the mitochondrial quality control system, which has implications for the development of therapeutic strategies.

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Section: Discussionmentioning

confidence: 99%

Mitochondrial Structure and Function in the Metabolic Myopathy Accompanying Patients with Critical Limb Ischemia

Groennebaek

Billeskov

Schytz

et al. 2020

Cells

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“…Remarkably, not only mitochondria but also lysosomes are crucial for an efficient mitophagy and the maintenance of mitohormesis. Recently, Triolo and Hood reviewed the beneficial effect of acute and chronic exercise in lysosomal biogenesis and reported that exercise might be a peculiar non-pharmacological "therapy" to clear disrupted cellular components [140]. In particular, the authors stressed that, after physical training in rodent models of lysosomal diseases such as Pompe disease and Danon syndrome, muscle mass and strength increased, while mitophagy and lysosomes production ameliorated.…”

Section: Exercise-an Anti-aging Strategy That Preserves Mitochondria mentioning

confidence: 99%

Impact of Melatonin on Skeletal Muscle and Exercise

Stacchiotti

Favero

Rodella

2020

Cells

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Skeletal muscle disorders are dramatically increasing with human aging with enormous sanitary costs and impact on the quality of life. Preventive and therapeutic tools to limit onset and progression of muscle frailty include nutrition and physical training. Melatonin, the indole produced at nighttime in pineal and extra-pineal sites in mammalians, has recognized anti-aging, anti-inflammatory, and anti-oxidant properties. Mitochondria are the favorite target of melatonin, which maintains them efficiently, scavenging free radicals and reducing oxidative damage. Here, we discuss the most recent evidence of dietary melatonin efficacy in age-related skeletal muscle disorders in cellular, preclinical, and clinical studies. Furthermore, we analyze the emerging impact of melatonin on physical activity. Finally, we consider the newest evidence of the gut–muscle axis and the influence of exercise and probably melatonin on the microbiota. In our opinion, this review reinforces the relevance of melatonin as a safe nutraceutical that limits skeletal muscle frailty and prolongs physical performance.

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“…Organelle degradation is mediated by autophagy, where double membrane vesicles known as autophagosomes engulf damaged organelles and fuse with a lysosomal membrane where these organelles are digested [28,49,57]. This process involves distinct steps, including induction, cargo recognition and selection, vesicle formation, autophagosome-vacuole fusion resulting in breakdown of the cargo, and the release of the degradation products back into the cytosol (Fig.…”

Section: General Autophagy Pathwaymentioning

confidence: 99%

“…It is well known that exercise has multiple beneficial health effects. Engaging in regular exercise facilitates an improvement in glucose homeostasis, cardiovascular health, the maintenance of muscle mass, and can help reduce complications that occur with aging [2,6,19,26,28,43,57]. On a molecular level, regular exercise exerts favorable effects on bioenergetics and nutrient delivery and uptake, which largely occur due to the accumulated adaptation of muscle in response to individual acute exercise bouts [18,19,48].…”

Section: Effect Of Acute Endurance Exercise On Mitophagymentioning

confidence: 99%

Mitophagy Regulation in Skeletal Muscle: Effect of Endurance Exercise and Age

Erlich

Hood

2019

J. of SCI. IN SPORT AND EXERCISE

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Mitochondria are essential energy-providing organelles that are required in the maintenance of healthy skeletal muscle. As such, the removal of damaged mitochondria, through mitophagy, is necessary to maintain mitochondrial quality. In aging muscle, mitochondrial content and function are often found to be reduced compared to young individuals. This occurs despite the fact that measures of mitophagy are elevated, suggesting that mitophagy is insufficiently high to remove all of the dysfunctional organelles in aging muscle. Recent evidence has shown that acute exercise promotes mitophagic signaling, leading to organelle degradation. This exercise-induced signaling is attenuated in aging muscle, suggesting that aging muscle loses its capacity for mitochondrial turnover in response to exercise. This contributes to the reduction in muscle health in elderly individuals. Chronic exercise training improves mitochondrial content and function, even in aging muscle, leading to reduced mitophagy signaling. Thus, exercise training should be prescribed for both young and elderly populations to promote the maintenance of a healthy mitochondrial pool, through the stimulation of both organelle biogenesis and mitophagy.

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Mitochondrial breakdown in skeletal muscle and the emerging role of the lysosomes

Cited by 31 publications

References 92 publications

Mitochondrial Structure and Function in the Metabolic Myopathy Accompanying Patients with Critical Limb Ischemia

Mitochondrial Structure and Function in the Metabolic Myopathy Accompanying Patients with Critical Limb Ischemia

Impact of Melatonin on Skeletal Muscle and Exercise

Mitophagy Regulation in Skeletal Muscle: Effect of Endurance Exercise and Age

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