Background and aims In mitochondrial myopathy, autophagy is presumed to play an important role in mitochondrial dysfunction. Rimmed vacuoles (RVs), a sign of autophagy, can be seen as a secondary phenomenon in muscle ragged-red fibres (RRFs), whereas the uncommon presentation is that some fibres contain RVs, but without any mitochondrial abnormalities. To investigate the pathogenesis beneath this pathological phenomenon.

Methods We reviewed 783 skeletal muscle specimens and selected five obtained from patients with suspected mitochondrial myopathy, characterised by clearly visible autophagic vacuoles in non-RRFs, besides the coexistence of RRFs and cytochrome oxidase-negative fibres. Immunohistochemical staining with LC-3, and electron microscopy studies were performed. Using resequencing microarray and a next-generation sequencing system, the mitochondrial DNA was screened for mutations and the heteroplasmic level was measured in skeletal muscle and blood.

Results Muscle fibres with RVs and RRFs, as well as some morphologically normal fibres, stained strongly for LC-3. Electron microscopy disclosed significant abnormal mitochondrial proliferation and existence of autophagic vacuoles. After mutation screening, m.8344A>G in the tRNA^Lys gene was detected in two patients. The heteroplasmy of mutated G was 45.1% in skeletal muscle and 17.8% in blood in patient 1; patient 2 exhibited 80.3% mutated G in skeletal muscle and 25.2% in blood.

Conclusions These findings demonstrate a new pathological phenotype for the m.8344A>G mutation- related disease and also provide pathological evidence of a correlation between mitochondrial abnormalities and autophagy.