1,721,338 research outputs found
Apoptotic signaling in skeletal muscle fibers during atrophy.
No full textThis brief review discusses an exciting area in skeletal muscle research, namely the role of apoptosis in relation to muscle activity. Apoptotic cell death appears to occur during atrophy as a mechanism for removing part of the myofiber without affecting its viability. Recent developments in our understanding of the signaling of muscle catabolism and new insights into the therapeutic outlets are highlighted. The roles of mitochondria, Ca2+, and tumor necrosis factor alpha in activating the caspase cascade are discussed. We speculate that atrophy-induced apoptosis is a normal regulatory process that the cell can use to reduce the number of organelles, thus ensuring optimal cell function
Protein breakdown in cancer cachexia.
No full textSkeletal muscle is a highly adaptive tissue, capable of altering muscle fiber size, functional capacity and metabolism in response to physiological stimuli. However, pathological conditions such as cancer growth compromise the mechanisms that regulate muscle homeostasis, resulting in loss of muscle mass, functional impairment and compromised metabolism. This tumor-induced condition is characterized by enhanced muscle protein breakdown and amino acids release that sustain liver gluconeogenesis and tissue protein synthesis. Proteolysis is controlled by the two most important cellular degradation systems, the ubiquitin proteasome and autophagy lysosome. These systems are carefully regulated by different signalling pathways that determine protein and organelle turnover. In this review we will describe the involvement of the ubiquitin proteasome and autophagy lysosome systems in cancer cachexia and the principal signalling pathways that regulate tumor-induced protein breakdown in muscle
Signaling in muscle atrophy and hypertrophy
No full textMuscle 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
Protein breakdown in muscle wasting: Role of autophagy-lysosome and ubiquitin-proteasome
No full textSkeletal 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 modulate the expression of rate-limiting enzymes of these proteolytic systems. The transcription factors FoxO3, which is 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: Muscle wasting
Autophagy in skeletal muscle
No full textMuscle 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
Autophagy in health and disease. 3. Involvement of autophagy in muscle atrophy
No full textLoss 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
New findings of lysosomal proteolysis in skeletal muscle
No full textPURPOSE OF REVIEW: To discuss the involvement of lysosomes in the control of muscle mass.
RECENT FINDINGS: Lysosomes control the half-life of long-lived proteins and the turnover of organelles and therefore, are critical for cellular homeostasis. Skeletal muscle contraction is a potential source of metabolic, mechanical, and thermal stressors. Therefore, the quality control of proteins and of organelles is particularly active in this tissue. Recent findings have shown that impairment of the degradation systems leads to accumulation of unfolded/misfolded proteins and altered organelles which turns into toxicity for the muscle cells. Conversely, excessive activation of proteolytic machinery, including lysosomal-dependent degradation, contributes to muscle loss, weakness, and finally to death. This article reviews the rapid progress made in the past few years regarding the role of lysosomal-dependent degradation in the homeostasis of adult muscle fibers.
SUMMARY: These findings will help to define the role of the lysosomal system in muscle homeostasis during physiological or pathological condition
FOXOphagy path to inducing stress resistance and cell survival
No full textNutrient 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
Memory or amnesia: the dilemma of stem cell therapy in muscular dystrophies.
No full textMuscular dystrophies are monogenetic diseases that are often characterized by the degeneration of both cardiac and skeletal muscle. Gene therapy to correct the mutated gene has shown promise in both animal models and clinical trials; however, current gene delivery strategies are limited to the introduction of the corrected gene into only one tissue. Strategies to target multiple striated muscle types would provide a much-needed improvement for the treatment of muscular dystrophies. In this issue of the JCI, Quattrocelli and colleagues demonstrate that induced pluripotent stem cells (iPSCs) with a myogenic propensity are able to engraft into both cardiac and skeletal muscles. The authors also identified a novel pool of mesodermal iPSC-derived progenitors (MiPs). Moreover, the authors show that these MiPs are amenable to gene correction and can restore function in murine dystrophic models. Together, the results of this study provide an important advance in improving gene delivery to treat patients with muscular dystrophy
Mitochondrial biogenesis and fragmentation as regulators of protein degradation in striated muscles
No full textMitochondria are dynamic organelles which adapt their morphology by fusion and fission events to the bioenergetic requirements of the cell. Cardiac and skeletal muscles are tissues with high energy demand and mitochondrial plasticity plays a key role in the homeostasis of these cells. Indeed, alterations in mitochondrial morphology, distribution and function are common features in catabolic conditions. Moreover, dysregulation of mitochondrial dynamics affects the signaling pathways that regulate muscle mass. This review discusses the recent findings of the role of mitochondrial fusion/fission and mitophagy in the control of proteolytic pathways
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