Increased intra-mitochondrial lipofuscin aggregates with spherical dense body formation in mitochondrial myopathy

Lipofuscin aggregation may result from incomplete degradation of damaged mitochondria by autophagy-lysosome pathway, and intra-mitochondrial lipofuscin aggregation may exacerbate mitochondrial abnormalities in mitochondrial myopathy (MM) and mitochondrial disease. We examined vastus lateralis muscle biopsies from 24 patients with pathologically diagnosed MM and clinically diagnosed chronic progressive external ophthalmoplegia, in comparison to the biopsies from 3 other groups:10 patients with inclusion body myositis (IBM), 11 younger adults, and 10 older subjects with no to minimal myopathic changes. Lipofuscin aggregation in muscle fibres was assessed on autofluorescence microscopy, some histochemical stains, and electron microscopy (EM). EM analyses demonstrated intra-mitochondrial lipofuscin aggregates, spherical dense bodies (SDBs), and paracrystalline inclusions (PCIs) which were semi-quantitatively assessed. Intra-mitochondrial lipofuscin aggregates showed no significant differences between groups of MM patients and older subjects or IBM patients, but significant differences between groups of younger adults and others with associated age-related changes. Intra-mitochondrial SDBs were significantly more in MM patients than in older subjects, IBM patients, and younger adults. There was a significant positive correlation between intra-mitochondrial lipofuscin aggregates and SDBs. These findings suggest that intra-mitochondrial formation of lipofuscin SDBs is more in MM and contributing to the pathophysiology of mitochondrial disease.