Mechanisms of protein degradation in atrophying muscles: What have we learned during the past decade?

Authors

Shenhav Shemer

Published in

The Journal of biological chemistry. Volume 302. Issue 3. Pages 111229. Epub Feb 03, 2026.

Abstract

Skeletal muscle atrophy occurs in diverse conditions, including aging, disuse, cancer cachexia, and chronic disease. It results from an imbalance between protein synthesis and degradation, where excessive proteolysis drives loss of contractile proteins, weakness, and metabolic decline. Recent advances in structural biology, multi-omics approaches, and high-resolution imaging have uncovered how sarcomeric and cytoskeletal components are gradually degraded by ubiquitin ligases, proteasomes, and autophagy. Mechanical loading and mechanotransduction emerge as key regulators of proteostasis, linking tension to anabolic signaling. Transcriptional and epigenetic control through IGF1-Akt-mTOR, TGF-β, inflammatory cytokines, and circadian rhythms, as well as non-coding RNAs and miRNAs, also contribute to wasting. This review summarizes these recent findings and novel therapeutic strategies, such as restoring mitochondrial function and modulating RNA networks and mechanosensitive signaling to preserve muscle mass and function.

PMID:
41643770
Bibliographic data and abstract were imported from PubMed on 14 Sep 2026.

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