Cellular and Molecular Mechanisms of Muscle Atrophy

Overview

Journal Dis Model Mech

Specialty General Medicine

Date 2012 Dec 27

PMID 23268536

Citations 605

Authors

Paolo Bonaldo

Marco Sandri

Affiliations

Soon will be listed here.

Abstract

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.

Citing Articles

Standardized Fingerroot () Extract Decelerates the Development of Sarcopenia in Aged Rats.

Kim C, Kang M, Kim Y, Hwang J Prev Nutr Food Sci. 2025; 30(1):47-55.

PMID: 40059920 PMC: 11884943. DOI: 10.3746/pnf.2025.30.1.47.

Resveratrol Attenuates Fibrosis and Alters Signaling Pathways in Diabetic Cardiac and Skeletal Muscles and Adipose Tissue Without Reversing Structural Damage.

Strunz C, Roggerio A, Cruz P, Benvenuti L, Irigoyen M, Mansur A Int J Mol Sci. 2025; 26(4).

PMID: 40004135 PMC: 11855909. DOI: 10.3390/ijms26041672.

Sarcopenia in Chronic Kidney Disease: A Narrative Review from Pathophysiology to Therapeutic Approaches.

Tsai C, Wang P, Hsiung T, Fan Y, Wu J, Kan W Biomedicines. 2025; 13(2).

PMID: 40002765 PMC: 11852367. DOI: 10.3390/biomedicines13020352.

Additive impact of metabolic syndrome and sarcopenia on all-cause and cause-specific mortality: an analysis of NHANES.

Zhang M, Zeng Q, Zhuang L Front Endocrinol (Lausanne). 2025; 15:1448395.

PMID: 39995525 PMC: 11847694. DOI: 10.3389/fendo.2024.1448395.

Mechanisms of muscle repair after peripheral nerve injury by electrical stimulation combined with blood flow restriction training.

Chu X, Sun J, Liang J, Liu W, Xing Z, Li Q Sports Med Health Sci. 2025; 7(3):173-184.

PMID: 39991124 PMC: 11846447. DOI: 10.1016/j.smhs.2024.10.002.

References

Bodine S, Latres E, Baumhueter S, Lai V, Nunez L, Clarke B . Identification of ubiquitin ligases required for skeletal muscle atrophy. Science. 2001; 294(5547):1704-8. DOI: 10.1126/science.1065874. View

Kline W, Panaro F, Yang H, Bodine S . Rapamycin inhibits the growth and muscle-sparing effects of clenbuterol. J Appl Physiol (1985). 2006; 102(2):740-7. DOI: 10.1152/japplphysiol.00873.2006. View

Shimizu N, Yoshikawa N, Ito N, Maruyama T, Suzuki Y, Takeda S . Crosstalk between glucocorticoid receptor and nutritional sensor mTOR in skeletal muscle. Cell Metab. 2011; 13(2):170-82. DOI: 10.1016/j.cmet.2011.01.001. View

Bothe G, Haspel J, Smith C, Wiener H, Burden S . Selective expression of Cre recombinase in skeletal muscle fibers. Genesis. 2000; 26(2):165-6. View

Izumiya Y, Hopkins T, Morris C, Sato K, Zeng L, Viereck J . Fast/Glycolytic muscle fiber growth reduces fat mass and improves metabolic parameters in obese mice. Cell Metab. 2008; 7(2):159-72. PMC: 2828690. DOI: 10.1016/j.cmet.2007.11.003. View

Demontis F, Perrimon N . FOXO/4E-BP signaling in Drosophila muscles regulates organism-wide proteostasis during aging. Cell. 2010; 143(5):813-25. PMC: 3066043. DOI: 10.1016/j.cell.2010.10.007. View

Li H, Kedar V, Zhang C, McDonough H, Arya R, Wang D . Atrogin-1/muscle atrophy F-box inhibits calcineurin-dependent cardiac hypertrophy by participating in an SCF ubiquitin ligase complex. J Clin Invest. 2004; 114(8):1058-71. PMC: 522252. DOI: 10.1172/JCI22220. View

Bello N, Lamsoul I, Heuze M, Metais A, Moreaux G, Calderwood D . The E3 ubiquitin ligase specificity subunit ASB2beta is a novel regulator of muscle differentiation that targets filamin B to proteasomal degradation. Cell Death Differ. 2009; 16(6):921-32. PMC: 2709956. DOI: 10.1038/cdd.2009.27. View

Kon M, Cuervo A . Chaperone-mediated autophagy in health and disease. FEBS Lett. 2009; 584(7):1399-404. PMC: 2843772. DOI: 10.1016/j.febslet.2009.12.025. View

10.

Gomes M, Lecker S, Jagoe R, Navon A, GOLDBERG A . Atrogin-1, a muscle-specific F-box protein highly expressed during muscle atrophy. Proc Natl Acad Sci U S A. 2001; 98(25):14440-5. PMC: 64700. DOI: 10.1073/pnas.251541198. View

11.

McPherron A, Lawler A, Lee S . Regulation of skeletal muscle mass in mice by a new TGF-beta superfamily member. Nature. 1997; 387(6628):83-90. DOI: 10.1038/387083a0. View

12.

Laplante M, Sabatini D . mTOR signaling in growth control and disease. Cell. 2012; 149(2):274-93. PMC: 3331679. DOI: 10.1016/j.cell.2012.03.017. View

13.

Kirkin V, Lamark T, Sou Y, Bjorkoy G, Nunn J, Bruun J . A role for NBR1 in autophagosomal degradation of ubiquitinated substrates. Mol Cell. 2009; 33(4):505-16. DOI: 10.1016/j.molcel.2009.01.020. View

14.

Goncalves M, Pistilli E, Balduzzi A, Birnbaum M, Lachey J, Khurana T . Akt deficiency attenuates muscle size and function but not the response to ActRIIB inhibition. PLoS One. 2010; 5(9):e12707. PMC: 2939888. DOI: 10.1371/journal.pone.0012707. View

15.

Dobrowolny G, Aucello M, Rizzuto E, Beccafico S, Mammucari C, Boncompagni S . Skeletal muscle is a primary target of SOD1G93A-mediated toxicity. Cell Metab. 2008; 8(5):425-36. DOI: 10.1016/j.cmet.2008.09.002. View

16.

Furuno K, Goodman M, GOLDBERG A . Role of different proteolytic systems in the degradation of muscle proteins during denervation atrophy. J Biol Chem. 1990; 265(15):8550-7. View

17.

Kitamura T, Ido Kitamura Y, Funahashi Y, Shawber C, Castrillon D, Kollipara R . A Foxo/Notch pathway controls myogenic differentiation and fiber type specification. J Clin Invest. 2007; 117(9):2477-85. PMC: 1950461. DOI: 10.1172/JCI32054. View

18.

Massague J, Seoane J, Wotton D . Smad transcription factors. Genes Dev. 2005; 19(23):2783-810. DOI: 10.1101/gad.1350705. View

19.

Kumar A, Bhatnagar S, Paul P . TWEAK and TRAF6 regulate skeletal muscle atrophy. Curr Opin Clin Nutr Metab Care. 2012; 15(3):233-9. PMC: 3397822. DOI: 10.1097/MCO.0b013e328351c3fc. View

20.

Youle R, Narendra D . Mechanisms of mitophagy. Nat Rev Mol Cell Biol. 2010; 12(1):9-14. PMC: 4780047. DOI: 10.1038/nrm3028. View