Basal mitophagy is widespread in Drosophila but minimally affected by loss of Pink1 or parkin.
Basal mitophagy is widespread in Drosophila but minimally affected by loss of Pink1 or parkin.
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DOI：
10.1083/jcb.201801044
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发表时间：
2018-05-07
期刊：
影响因子：
--
通讯作者：
Whitworth AJ
中科院分区：
文献类型：
--
作者：
Lee JJ;Sanchez-Martinez A;Martinez Zarate A;Benincá C;Mayor U;Clague MJ;Whitworth AJ
PINK 1/parkin是体外应激诱导的线粒体自噬的关键介质，但其对体内基础线粒体自噬的影响尚不清楚。新的果蝇报告细胞系揭示了许多组织中丰富的线粒体自噬，包括多巴胺能神经元，这不受PINK 1/parkin丢失的影响。帕金森病因子PINK 1和parkin在体外应激诱导的线粒体自噬中有很强的牵连，但关于它们在体内对基础线粒体自噬的影响知之甚少。我们产生了转基因表达荧光线粒体自噬报告基因的果蝇，以评估生理条件下Pink 1/parkin突变对基础线粒体自噬的影响。我们发现，线粒体自噬是很容易检测和丰富的许多组织，包括帕金森病相关的多巴胺能神经元。但在飞行肌中未检测到线粒体溶酶体。令人惊讶的是，在Pink 1或parkin null果蝇中，我们没有观察到对基础线粒体自噬的任何实质性影响。由于这些果蝇表现出运动缺陷和多巴胺能神经元损失，我们的研究结果提出了与PINK 1/parkin通路相关的致病机制的当前假设的问题。我们的研究结果提供的证据表明，Pink 1和parkin是不必要的散装基础线粒体自噬在果蝇。他们还强调，基础线粒体自噬的机制仍然很大程度上不清楚。
PINK1/parkin are key mediators of stress-induced mitophagy in vitro, but their impact on basal mitophagy in vivo is unclear. Novel Drosophila reporter lines reveal abundant mitophagy in many tissues, including dopaminergic neurons, that is unaffected by loss of PINK1/parkin. 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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影响因子：
16.2
作者：
Pickrell AM;Youle RJ
通讯作者：
Youle RJ
DOI：
10.1083/jcb.201401070
发表时间：
2014-09-01
期刊：
The Journal of cell biology
影响因子：
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作者：
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通讯作者：
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DOI：
10.1111/febs.14336
发表时间：
2018-04
期刊：
The FEBS journal
影响因子：
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作者：
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通讯作者：
Ganley IG
DOI：
10.1083/jcb.201603039
发表时间：
2016-08-01
期刊：
The Journal of cell biology
影响因子：
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作者：
McWilliams TG;Prescott AR;Allen GF;Tamjar J;Munson MJ;Thomson C;Muqit MM;Ganley IG
通讯作者：
Ganley IG
影响因子：
8.8
作者：
Lee Y;Stevens DA;Kang SU;Jiang H;Lee YI;Ko HS;Scarffe LA;Umanah GE;Kang H;Ham S;Kam TI;Allen K;Brahmachari S;Kim JW;Neifert S;Yun SP;Fiesel FC;Springer W;Dawson VL;Shin JH;Dawson TM
通讯作者：
Dawson TM