Clin Exp Rheumatol. 2026 Feb;44(2):
384-389
OBJECTIVES: Idiopathic inflammatory myopathies (IIMs) are a heterogeneous group of acquired muscle disorders characterised by immune-mediated muscle damage and systemic involvement. Increasing evidence highlights mitochondrial abnormalities as a key contributor to muscle weakness, inflammation, and disease progression. This review aims to summarise current knowledge on the mechanisms, histopathological features, and clinical implications of mitochondrial dysfunction in IIMs, as well as to discuss emerging therapeutic strategies targeting mitochondrial impairment.
METHODS: A narrative review of the literature was conducted using PubMed, with no temporal restrictions. Only English-language articles were included. Search terms comprised "inflammatory myopathies," "mitochondrial abnormalities," and "mitochondrial antibodies AND inflammatory myopathies." Studies addressing mitochondrial structure and function, histopathological findings, autoantibodies targeting mitochondrial components, and therapeutic approaches in IIMs were selected and analysed.
RESULTS: Mitochondrial dysfunction in IIMs involves impaired oxidative phosphorylation, increased oxidative stress, disrupted calcium homeostasis, defective mitophagy, and mitochondrial DNA damage. Histopathological findings include cytochrome c oxidase-negative fibres, ragged red fibres, abnormal mitochondrial morphology, and altered mitochondrial distribution, particularly prominent in inclusion body myositis. Inflammatory mechanisms further exacerbate mitochondrial injury through cytokine signalling, cytotoxic immune responses, and interferon-mediated pathways. Autoantibodies targeting mitochondrial components, such as anti-NDUFA11 and anti-mitochondrial antibodies, define subgroups with more severe or refractory disease. Therapeutic strategies reducing inflammation may indirectly improve mitochondrial function, while novel approaches, including interferon blockade, mitochondrial transplantation, and exercise-based interventions, show promise in restoring bioenergetics.
CONCLUSIONS: Mitochondrial dysfunction represents a central pathogenic mechanism in IIMs, tightly interwoven with immune-mediated muscle damage. Targeting both inflammatory and mitochondrial pathways may offer more effective and personalised therapeutic strategies for patients with inflammatory myopathies.