Medical Research Council Mitochondrial Biology Unit, University of Cambridge, Cambridge, England, UK.
Department of Biochemistry and Molecular Biology, University of the Basque Country, Leioa-Bizkaia, Spain.
J Cell Biol. 2018 May 7;217(5):1613-1622. doi: 10.1083/jcb.201801044. Epub 2018 Mar 2.
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 expressing fluorescent mitophagy reporters to evaluate the impact of 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 or 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 They also emphasize that mechanisms underpinning basal mitophagy remain largely obscure.
帕金森病相关因子 PINK1 和 parkin 被强烈认为与体外应激诱导的线粒体自噬有关,但对于它们对体内基础线粒体自噬的影响知之甚少。我们生成了表达荧光线粒体自噬报告基因的转基因 ,以评估 突变对生理条件下基础线粒体自噬的影响。我们发现,线粒体自噬在许多组织中都很容易被检测到,包括与帕金森病相关的多巴胺能神经元。然而,我们在飞行肌中没有检测到线粒体溶酶体。令人惊讶的是,在 或 缺失的果蝇中,我们没有观察到基础线粒体自噬有任何实质性的影响。由于这些果蝇表现出运动缺陷和多巴胺能神经元丧失,我们的发现对与 PINK1/parkin 通路相关的致病机制的现有假设提出了质疑。我们的研究结果表明,Pink1 和 parkin 对于 中的基础线粒体自噬并非必需的。它们还强调,基础线粒体自噬的机制在很大程度上仍不清楚。