Dysregulated mitophagy has been linked to Parkinson's disease (PD) due to the role of PTEN-induced kinase 1 (PINK1) in mediating depolarization-induced mitophagy in vitro. Elegant mouse reporters have revealed the pervasive nature of basal mitophagy in vivo, yet the role of PINK1 and tissue metabolic context remains unknown. Using mito-QC, we investigated the contribution of PINK1 to mitophagy in metabolically active tissues. We observed a high degree of mitophagy in neural cells, including PD-relevant mesencephalic dopaminergic neurons and microglia. In all tissues apart from pancreatic islets, loss of Pink1 did not influence basal mitophagy, despite disrupting depolarization-induced Parkin activation. Our findings provide the first in vivo evidence that PINK1 is detectable at basal levels and that basal mammalian mitophagy occurs independently of PINK1. This suggests multiple, yet-to-be-discovered pathways orchestrating mammalian mitochondrial integrity in a context-dependent fashion, and this has profound implications for our molecular understanding of vertebrate mitophagy.

中文翻译：

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基础线粒体自噬在高代谢需求的小鼠组织中独立于 PINK1 发生。

由于 PTEN 诱导的激酶 1 (PINK1) 在体外介导去极化诱导的线粒体自噬中的作用，失调的线粒体自噬与帕金森病 (PD) 相关。优雅的小鼠记者揭示了体内基础线粒体自噬的普遍性质，但 PINK1 和组织代谢环境的作用仍然未知。使用 mito-QC，我们研究了 PINK1 对代谢活跃组织中线粒体自噬的贡献。我们观察到神经细胞中高度的线粒体自噬，包括与 PD 相关的中脑多巴胺能神经元和小胶质细胞。在除胰岛外的所有组织中，Pink1 的缺失不影响基底线粒体自噬，尽管破坏了去极化诱导的 Parkin 激活。我们的研究结果提供了第一个体内证据，证明 PINK1 在基础水平上是可检测的，并且基础哺乳动物线粒体自噬独立于 PINK1 发生。这表明有多种尚未发现的通路以依赖于环境的方式协调哺乳动物线粒体完整性，这对我们对脊椎动物线粒体自噬的分子理解具有深远的影响。