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Basal mitophagy is widespread in Drosophila but minimally affected by loss of Pink1 or parkin.

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Peer-reviewed

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Abstract

The Parkinson's disease factors PINK1 and parkin are strongly implicated in stress-induced mitophagy in vitro, but little is known about their impact on basal mitophagy in vivo. We generated transgenic Drosophila melanogaster expressing fluorescent mitophagy reporters to evaluate the impact of Pink1/parkin mutations on basal mitophagy under physiological conditions. We find that mitophagy is readily detectable and abundant in many tissues, including Parkinson's disease-relevant dopaminergic neurons. However, we did not detect mitolysosomes in flight muscle. Surprisingly, in Pink1 or parkin null flies, we did not observe any substantial impact on basal mitophagy. Because these flies exhibit locomotor defects and dopaminergic neuron loss, our findings raise questions about current assumptions of the pathogenic mechanism associated with the PINK1/parkin pathway. Our findings provide evidence that Pink1 and parkin are not essential for bulk basal mitophagy in Drosophila They also emphasize that mechanisms underpinning basal mitophagy remain largely obscure.

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Keywords

Lysosomes, Animals, Drosophila melanogaster, Ubiquitin-Protein Ligases, Protein-Serine-Threonine Kinases, Drosophila Proteins, Reproducibility of Results, Organ Specificity, Larva, Mutation, Genes, Reporter, Mitophagy

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Sponsorship
European Commission FP7 ERC Starting Independent Researcher Grant (SIRG) (309742)
MRC (MC_UP_1501/1)
MRC (MC_UU_00015/6)