Emerging Mechanisms of Skeletal Muscle Homeostasis and Cachexia: The SUMO Perspective

Sep 24, 2026

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Mobility is a fundamental feature of animal life and strongly shapes evolutionary success, while skeletal muscle is the main driver of voluntary movement. Beyond motion, skeletal muscle governs glucose, amino-acid, and lipid homeostasis, and its atrophy disrupts steady-state muscle physiology. Cachexia is a multifactorial wasting syndrome marked by extreme loss of skeletal muscle mass, poor life quality, and over 30% mortality in advanced cancer patients. This review summarizes regulatory mechanisms supporting muscle function and how they become dysregulated in wasting syndromes, emphasizing SUMO-mediated protein posttranslational control and potential therapeutic strategies.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages21

Reading Time53 min

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Abstract

Introduction

Skeletal muscle structure and functions

Muscle wasting disorders: sarcopenia and cachexia

cells Review Emerging Mechanisms of Skeletal Muscle Homeostasis and Cachexia: The SUMO Perspective Bushra Khan †, Luis Vincens Gand†, Mamta Amrute-Nayak and Arnab Nayak * Citation: Khan, B.; Gand, L.V.; Amrute-Nayak, M.; Nayak, A. Emerging Mechanisms of Skeletal Muscle Homeostasis and Cachexia: The SUMO Perspective. Cells 2023, 12, 644. [https://doi.org/10.3390/](https://doi.org/10.3390/)[ ](https://doi.org/10.3390/)cells12040644 Academic Editor: Kunihiro Sakuma Received: 30 November 2022 Revised: 10 February 2023 Accepted: 14 February 2023 Published: 17 February 2023 Copyright: © 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ([https://](https://)[ ](https://)[creativecommons.org/licenses/by/](creativecommons.org/licenses/by/)[ ](creativecommons.org/licenses/by/)[4.0/](4.0/)) . Institute of Molecular and Cell Physiology, Hannover Medical School, Carl-Neuberg-Str. 1, 30625 Hannover, Germany * Correspondence: nayak.arnab@mh-hannover.de † These authors contributed equally to this work. Abstract: Mobility is an intrinsic feature of the animal kingdom that stimulates evolutionary processes and determines the biological success of animals. Skeletal muscle is the primary driver of voluntary movements. Besides, skeletal muscles have an immense impact on regulating glucose, amino acid, and lipid homeostasis. Muscle atrophy/wasting conditions are accompanied by a drastic effect on muscle function and disrupt steady-state muscle physiology. Cachexia is a complex multifactorial muscle wasting syndrome characterized by extreme loss of skeletal muscle mass, resulting in a dramatic decrease in life quality and reported mortality in more than 30% of patients with advanced cancers. The lack of directed treatments to prevent or relieve muscle loss indicates our inadequate knowledge of molecular mechanisms involved in muscle cell organization and the molecular etiology of cancerinduced cachexia (CIC) . This review highlights the latest knowledge of regulatory mechanisms involved in maintaining muscle function and their deregulation in wasting syndromes, particularly in cachexia. Recently, protein posttranslational modiﬁcation by the small ubiquitin-like modiﬁer (SUMO) has emerged as a key regulatory mechanism of protein function with implications for different aspects of cell physiology and diseases. We also review an atypical association of SUMO-mediated pathways in this context and deliberate on potential treatment strategies to alleviate muscle atrophy. Keywords: sarcomere; muscle atrophy; cachexia; muscle metabolism; chromatin signaling; ubiquitination; ubiquitin-like modiﬁers; SUMO-speciﬁc isopeptidase 1. Introduction Skeletal muscle is an astounding organ constituting over 650 muscles accounting for approximately 40% of total body mass and up to 30% of basal energy expenditure [1] . The skeletal muscle is made up of muscle cells, comprising several myoﬁbrils. The myoﬁbrils contain linear arrays of contractile units, the sarcomere. The precisely organized sarcomeres consist of myosin-based thick ﬁlaments and actin-based thin ﬁlaments, which are further supported by macromolecular proteins, such as titin and nebulin along the ﬁlamentsand protein complexes residing in Z-bands. The region between two Z-bands deﬁne the length of one sarcomeric unit, which is approximately 2.2 􀀖m in the case of human skeletal muscle. According to the sliding ﬁlament model [2], the thick and thin ﬁlaments slide past each other, whereby the ATP-driven cyclical interaction between the actin and myosin ﬁlaments causes the muscle shortening, generating the force necessary for movements atthe molecular as well as organismic level. Muscle contraction upon neural stimulation is responsible for driving the movements, maintaining balance, regulating body posture, breathing, and controlling the b

FAQs

What role does skeletal muscle play in overall physiology?

Skeletal muscle drives voluntary movements and also regulates glucose, amino-acid, and lipid homeostasis, linking muscle health to whole-body metabolism.

What is cachexia and why is it clinically important?

Cachexia is a complex, multifactorial muscle-wasting syndrome characterized by extreme loss of skeletal muscle mass, leading to dramatically reduced life quality and reported mortality in more than 30% of patients with advanced cancers.

Why is SUMO highlighted as a key mechanism in this review?

SUMO-mediated protein posttranslational modifications are presented as an emerging key regulatory mechanism of protein function, with implications for multiple aspects of cell physiology and disease, including wasting contexts.

Sep 24, 2026

Uploaded by acoobca