Skeletal muscle adapts its mass as consequence of physical activity, metabolism and hormones. Catabolic conditions or inactivity induce signaling pathways that regulate the process of muscle loss. ...Muscle atrophy in adult tissue occurs when protein degradation rates exceed protein synthesis. Two major protein degradation pathways, the ubiquitin-proteasome and the autophagy-lysosome systems, are activated during muscle atrophy and variably contribute to the loss of muscle mass. These degradation systems are controlled by a transcription dependent program that modulates the expression of rate-limiting enzymes of these proteolytic systems. The transcription factors FoxO, which are negatively regulated by Insulin-Akt pathway, and NF-κB, which is activated by inflammatory cytokines, were the first to be identified as critical for the atrophy process. In the last years a variety of pathways and transcription factors have been found to be involved in regulation of atrophy. This review will focus on the last progress in ubiquitin-proteasome and autophagy-lysosome systems and their involvement in muscle atrophy. This article is part of a Directed Issue entitled: Molecular basis of muscle wasting.
Autophagy in skeletal muscle Sandri, Marco
FEBS letters,
April 02, 2010, Letnik:
584, Številka:
7
Journal Article
Recenzirano
Odprti dostop
Muscle mass represents 40–50% of the human body and, in mammals, is one of the most important sites for the control of metabolism. Moreover, during catabolic conditions, muscle proteins are mobilized ...to sustain gluconeogenesis in the liver and to provide alternative energy substrates for organs. However, excessive protein degradation in the skeletal muscle is detrimental for the economy of the body and it can lead to death. The ubiquitin-proteasome and autophagy-lysosome systems are the major proteolytic pathways of the cell and are coordinately activated in atrophying muscles. However, the role and regulation of the autophagic pathway in skeletal muscle is still largely unknown. This review will focus on autophagy and discuss its beneficial or detrimental role for the maintenance of muscle mass.
Muscle performance is influenced by turnover of contractile proteins. Production of new myofibrils and degradation of existing proteins is a delicate balance, which, depending on the condition, can ...promote muscle growth or loss. Protein synthesis and protein degradation are coordinately regulated by pathways that are influenced by mechanical stress, physical activity, availability of nutrients, and growth factors. Understanding the signaling that regulates muscle mass may provide potential therapeutic targets for the prevention and treatment of muscle wasting in metabolic and neuromuscular diseases.
Loss of muscle mass aggravates a variety of diseases, and understanding the molecular mechanisms that control muscle wasting is critical for developing new therapeutic approaches. Weakness is caused ...by loss of muscle proteins, and recent studies have underlined a major role for the autophagy-lysosome system in regulating muscle mass. Some key components of the autophagy machinery are transcriptionally upregulated during muscle wasting, and their induction precedes muscle loss. However, it is unclear whether autophagy is detrimental, causing atrophy, or beneficial, promoting survival during catabolic conditions. This review discusses recent findings on signaling pathways regulating autophagy.
Skeletal muscle is the protein reservoir of our body and an important regulator of glucose and lipid homeostasis. Consequently, the growth or the loss of muscle mass can influence general metabolism, ...locomotion, eating and respiration. Therefore, it is not surprising that excessive muscle loss is a bad prognostic index of a variety of diseases ranging from cancer, organ failure, infections and unhealthy ageing. Muscle function is influenced by different quality systems that regulate the function of contractile proteins and organelles. These systems are controlled by transcriptional dependent programs that adapt muscle cells to environmental and nutritional clues. Mechanical, oxidative, nutritional and energy stresses, as well as growth factors or cytokines modulate signaling pathways that, ultimately, converge on protein and organelle turnover. Novel insights that control and orchestrate such complex network are continuously emerging and will be summarized in this review. Understanding the mechanisms that control muscle mass will provide therapeutic targets for the treatment of muscle loss in inherited and non-hereditary diseases and for the improvement of the quality of life during ageing.
The loss of skeletal muscle mass under a wide range of acute and chronic maladies is associated with poor prognosis, reduced quality of life, and increased mortality. Decades of research indicate the ...importance of skeletal muscle for whole body metabolism, glucose homeostasis, as well as overall health and wellbeing. This tissue's remarkable ability to rapidly and effectively adapt to changing environmental cues is a double-edged sword. Physiological adaptations that are beneficial throughout life become maladaptive during atrophic conditions. The atrophic program can be activated by mechanical, oxidative, and energetic distress, and is influenced by the availability of nutrients, growth factors, and cytokines. Largely governed by a transcription-dependent mechanism, this program impinges on multiple protein networks including various organelles as well as biosynthetic and quality control systems. Although modulating muscle function to prevent and treat disease is an enticing concept that has intrigued research teams for decades, a lack of thorough understanding of the molecular mechanisms and signaling pathways that control muscle mass, in addition to poor transferability of findings from rodents to humans, has obstructed efforts to develop effective treatments. Here, we review the progress made in unraveling the molecular mechanisms responsible for the regulation of muscle mass, as this continues to be an intensive area of research.
Loss of muscle mass and force occurs in many diseases such as disuse/inactivity, diabetes, cancer, renal, and cardiac failure and in aging-sarcopenia. In these catabolic conditions the mitochondrial ...content, morphology and function are greatly affected. The changes of mitochondrial network influence the production of reactive oxygen species (ROS) that play an important role in muscle function. Moreover, dysfunctional mitochondria trigger catabolic signaling pathways which feed-forward to the nucleus to promote the activation of muscle atrophy. Exercise, on the other hand, improves mitochondrial function by activating mitochondrial biogenesis and mitophagy, possibly playing an important part in the beneficial effects of physical activity in several diseases. Optimized mitochondrial function is strictly maintained by the coordinated activation of different mitochondrial quality control pathways. In this review we outline the current knowledge linking mitochondria-dependent signaling pathways to muscle homeostasis in aging and disease and the resulting implications for the development of novel therapeutic approaches to prevent muscle loss.
Skeletal muscle is a plastic organ that is maintained by multiple pathways regulating cell and protein turnover. During muscle atrophy, proteolytic systems are activated, and contractile proteins and ...organelles are removed, resulting in the shrinkage of muscle fibers. Excessive loss of muscle mass is associated with poor prognosis in several diseases, including myopathies and muscular dystrophies, as well as in systemic disorders such as cancer, diabetes, sepsis and heart failure. Muscle loss also occurs during aging. In this paper, we review the key mechanisms that regulate the turnover of contractile proteins and organelles in muscle tissue, and discuss how impairments in these mechanisms can contribute to muscle atrophy. We also discuss how protein synthesis and degradation are coordinately regulated by signaling pathways that are influenced by mechanical stress, physical activity, and the availability of nutrients and growth factors. Understanding how these pathways regulate muscle mass will provide new therapeutic targets for the prevention and treatment of muscle atrophy in metabolic and neuromuscular diseases.
The dynamic coordination of processes controlling the quality of the mitochondrial network is crucial to maintain the function of mitochondria in skeletal muscle. Changes of mitochondrial proteolytic ...system, dynamics (fusion/fission), and mitophagy induce pathways that affect muscle mass and performance. When muscle mass is lost, the risk of disease onset and premature death is dramatically increased. For instance, poor quality of muscles correlates with the onset progression of several age-related disorders such as diabetes, obesity, cancer, and aging sarcopenia. To date, there are no drug therapies to reverse muscle loss, and exercise remains the best approach to improve mitochondrial health and to slow atrophy in several diseases. This review will describe the principal mechanisms that control mitochondrial quality and the pathways that link mitochondrial dysfunction to muscle mass regulation.
Nutrient deprivation and other stress stimuli elicit metabolic changes (such as the induction of autophagy and activation of FOXO transcription factors) that help an organism adapt to stressful ...conditions. A link between these stress response pathways is revealed by the finding that FOXO3 upregulates the expression of glutamine synthetase to promote glutamine accumulation, inhibit mTOR signalling and promote autophagy.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
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