2. Academic Validation
  3. Discovery of the novel autophagy inhibitor aumitin that targets mitochondrial complex I

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

  • Chem Sci. 2018 Feb 26;9(11):3014-3022. 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
Affiliations

Affiliations

  • 1 Max-Planck-Institute of Molecular Physiology , Department of Chemical Biology , Otto-Hahn-Str. 11 , 44227 Dortmund , Germany.
  • 2 Faculty of Chemistry and Chemical Biology , TU Dortmund University , Otto-Hahn-Str. 4a , 44227 Dortmund , Germany . Email: herbert.waldmann@mpi-dortmund.mpg.de.
  • 3 RIKEN-Max Planck Joint Research Division for Systems Chemical Biology , RIKEN CSRS , 2-1, Hirosawa, Wako , Saitama 351-0198 , Japan.
  • 4 Chemical Biology Research Group , RIKEN CSRS , 2-1, Hirosawa, Wako , Saitama 351-0198 , Japan.
  • 5 Chemical Genomics Centre of the Max-Planck-Society , Otto-Hahn-Str. 15 , 44227 Dortmund , Germany.
  • 6 Bio-Active Compounds Discovery Research Unit , RIKEN CSRS , 2-1, Hirosawa, Wako , Saitama 351-0198 , Japan.
PMID: 29732085 DOI: 10.1039/c7sc05040b
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.

Figures
Products