University of Helsinki: New disease mechanism behind mitochondrial diseases identified

The role of mitophagy in the pathogenesis of diseases has been unknown until now. A recent study shows that deficient mitophagy – recycling of mitochondria in cells – causes human disease.

An explanation for the abnormal muscle fibres
A team of investigators, led by academy professor Anu Suomalainen Wartiovaara with assistant professor Thomas McWilliams in Helsinki University in collaboration with Newcastle University, has developed a method allowing analysis of mitochondrial recycling inside a diseased muscle.

The investigators report that in mice and patients with mitochondrial disease a single muscle can have myofibers with a mild or severe disease-stage or be normal. Such fibers can exist side-by-side, forming a mosaic-like pattern.

The fibers with mild disease have high mitophagic activity that enables recycling of damaged mitochondria. In a more progressed disease-stage mitophagy is stalled, and damaged mitochondria fill these myofibers. Such fibers are called ragged-red fibers, hallmarks of mitochondrial disease pathology, and occurring also in low amounts in normal aging.

“The findings show that stalled mitophagy is the mechanism underlying ragged-red fibers,” explains Suomalainen Wartiovaara.

From cellular research to treatment
The results showed that pharmacological activation of mitophagy reversed the progression of mitochondrial muscle disease.

“It is exciting that disease-related damage could be partially removed by pharmacological treatment that activated mitophagy,” says Suomalainen Wartiovaara.

The investigators used the drug rapamycin which is used in medicine e.g. to prevent rejection of transplanted organs. Rapamycin has, however, unwanted side-effects, including suppression of immunological defense mechanisms. Therefore it is not the best possible treatment.

“The evidence proposes usefulness of specific mitophagy activator compounds for treating mitochondrial diseases as well as aging-related mitochondrial dysfunction,” Suomalainen Wartiovaara confirms.

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