Deciphering molecular mechanisms underlying the unconventional extracellular mitochondria release

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Selective removal of damaged mitochondria by mitophagy is crucial for maintaining mitochondrial quality control and cell viability. Here we demonstrate an alternative quality control pathway mediated by extracellular mitochondria release. We performed real time tracking of fluorescence-labelled mitochondria in cultured cells and observed release of mitochondria into extracellular space. Using mitochondrial toxin treatment and parkin gene overexpression and knockdown approaches, we found that mitochondrial stress and perturbation of mitophagy induce greater extracellular mitochondria release. Remarkably, fibroblasts and CSF from Parkinson’s disease patients carrying parkin mutations showed increased extracellular mitochondria release compared to control subjects, providing evidence in clinical context that impairment of conventional mitophagy prompts the alternative pathway.