Discovery of the novel autophagy inhibitor aumitin that targets mitochondrial complex I†,Chemical Science

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Discovery of the novel autophagy inhibitor aumitin that targets mitochondrial complex I†
Chemical Science ( IF 7.6 ) Pub Date : 2018-02-26 00:00:00 , DOI: 10.1039/c7sc05040b
Lucas Robke _{1,

2,

3} , Yushi Futamura ₄ , Georgios Konstantinidis ₅ , Julian Wilke _{1,

2} , Harumi Aono ₄ , Zhwan Mahmoud ₂ , Nobumoto Watanabe _{3,

6} , Yao-Wen Wu ₅ , Hiroyuki Osada _{3,

4} , Luca Laraia ₁ , Herbert Waldmann _{1,

2}

Affiliation

Macroautophagy is a conserved eukaryotic process for degradation of cellular components in response to lack of nutrients. It is involved in the development of diseases, notably cancer and neurological disorders including Parkinson's disease. Small molecule autophagy modulators have proven to be valuable tools to dissect and interrogate this crucial metabolic pathway and are in high demand. Phenotypic screening for autophagy inhibitors led to the discovery of the novel autophagy inhibitor aumitin. Target identification and confirmation revealed that aumitin inhibits mitochondrial respiration by targeting complex I. We show that inhibition of autophagy by impairment of mitochondrial respiration is general for several mitochondrial inhibitors that target different mitochondrial complexes. Our findings highlight the importance of mitochondrial respiration for autophagy regulation.

中文翻译：

发现针对线粒体复合物 I 的新型自噬抑制剂 aumitin†

巨自噬是一种保守的真核过程，用于响应营养缺乏而降解细胞成分。它涉及疾病的发展，特别是癌症和神经系统疾病，包括帕金森病。小分子自噬调节剂已被证明是剖析和探究这一关键代谢途径的宝贵工具，并且需求量很大。自噬抑制剂的表型筛选导致了新型自噬抑制剂aumitin的发现。靶点识别和确认表明，aumitin 通过靶向复合物 I 来抑制线粒体呼吸。我们发现，通过损害线粒体呼吸来抑制自噬对于针对不同线粒体复合物的几种线粒体抑制剂来说是普遍的。我们的研究结果强调了线粒体呼吸对于自噬调节的重要性。

更新日期：2018-02-26

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