# Mitochondrial defects in sporadic inclusion body myositis—causes and consequences

## TL;DR

This paper explores how mitochondrial defects may contribute to the development of sporadic inclusion body myositis, a muscle disease resistant to standard treatments.

## Contribution

The paper highlights mitochondrial dysfunction as a potential overlooked cause of sIBM and suggests mitochondrial-targeted treatments as a novel therapeutic approach.

## Key findings

- Mitochondrial defects are more severe in sIBM compared to other inflammatory myopathies.
- Mitochondrial DNA deletions and protein aggregation contribute to mitochondrial dysfunction in sIBM.
- Mitochondrial damage may trigger immune responses and programmed cell death in sIBM.

## Abstract

Sporadic inclusion body myositis (sIBM) is a distinct subcategory of Idiopathic Inflammatory Myopathies (IIM), characterized by unique pathological features such as muscle inflammation, rimmed vacuoles, and protein aggregation within the myofibers. Although hyperactivation of the immune system is widely believed as the primary cause of IIM, it is debated whether non-immune tissue dysfunction might contribute to the disease’s onset as patients with sIBM are refractory to conventional immunosuppressant treatment. Moreover, the findings that mitochondrial dysfunction can elicit non-apoptotic programmed cell death and the subsequent immune response further support this hypothesis. Notably, abnormal mitochondrial structure and activities are more prominent in the muscle of sIBM than in other types of IIM, suggesting the presence of defective mitochondria might represent an overlooked contributor to the disease onset. The large-scale mitochondrial DNA deletion, aberrant protein aggregation, and slowed organelle turnover have provided mechanistic insights into the genesis of impaired mitochondria in sIBM. This article reviews the disease hallmarks of sIBM, the plausible contributors of mitochondrial damage in the sIBM muscle, and the immunological responses associated with mitochondrial perturbations. Additionally, the potential application of mitochondrial-targeted chemicals as a new treatment strategy to sIBM is explored and discussed.