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

基础线粒体自噬在果蝇中广泛存在,但 Pink1 或 parkin 的缺失对其影响很小

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作者:Juliette J Lee, Alvaro Sanchez-Martinez, Aitor Martinez Zarate #, Cristiane Benincá, Ugo Mayor, Michael J Clague, Alexander J Whitworth

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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