Issue 11, 2018

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

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.

Graphical abstract: Discovery of the novel autophagy inhibitor aumitin that targets mitochondrial complex I

Supplementary files

Article information

Article type
Edge Article
Submitted
24 Nov 2017
Accepted
20 Feb 2018
First published
26 Feb 2018
This article is Open Access

All publication charges for this article have been paid for by the Royal Society of Chemistry
Creative Commons BY license

Chem. Sci., 2018,9, 3014-3022

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

L. Robke, Y. Futamura, G. Konstantinidis, J. Wilke, H. Aono, Z. Mahmoud, N. Watanabe, Y. Wu, H. Osada, L. Laraia and H. Waldmann, Chem. Sci., 2018, 9, 3014 DOI: 10.1039/C7SC05040B

This article is licensed under a Creative Commons Attribution 3.0 Unported Licence. You can use material from this article in other publications without requesting further permissions from the RSC, provided that the correct acknowledgement is given.

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