Current Progress in the Role of Ferroptosis in Skeletal Muscle Atrophy

Atrophy of skeletal muscles, caused by multiple factors, including ageing, disuse, trauma and systemic diseases, is a major pathological condition that affects physical performance and systemic health by the loss of muscle function; in effect, weakening the whole body and leading to disabling conditions such as sarcopenia, frailty and increased fall risk. First reported in 2012 by Dixon et al., ferroptosis is a newly identified, distinct type of regulated cell death characterised by unique biochemical and morphological features and differs from classic apoptosis and necrosis. One hallmark feature of ferroptosis is its iron-dependence: excessive free intracellular iron deposits catalyse rapid peroxidation of membrane lipids, and release cytotoxic lipid peroxides, which interfere with cell integrity. In recent years, significant progress has been made in elucidating the roles of ferroptosis-related pathways in skeletal muscle atrophy. Building on these advances, our review systematizes skeletal muscle atrophy into three significant categories: ageing-, disuse- and systemic disease-induced atrophy. It carefully explores the involvement of ferroptosis in each of these atrophy models. Moreover, this review identifies and discusses key ferroptosis-related molecular targets for consideration, aiming to provide insights and possible future directions for developing therapies to treat muscle-wasting disorders.