Discovery of the novel autophagy inhibitor aumitin that targets mitochondrial complex i

Lucas Robke, Yushi Futamura, Georgios Konstantinidis, Julian Wilke, Harumi Aono, Zhwan Mahmoud, Nobumoto Watanabe, Yao Wen Wu, Hiroyuki Osada, Luca Laraia, Herbert Waldmann*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

20 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)3014-3022
Number of pages9
JournalChemical Science
Volume9
Issue number11
DOIs
Publication statusPublished - 2018
Externally publishedYes

ASJC Scopus subject areas

  • Chemistry(all)

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