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Modulation of autophagy by the novel mitochondrial complex I inhibitor Authipyrin
Umeå University, Faculty of Science and Technology, Department of Chemistry.
Umeå University, Faculty of Science and Technology, Department of Chemistry.
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2019 (English)In: Bioorganic & Medicinal Chemistry, ISSN 0968-0896, E-ISSN 1464-3391, Vol. 27, no 12, p. 2444-2448Article in journal (Refereed) Published
Abstract [en]

Autophagy ensures cellular homeostasis by the degradation of long-lived proteins, damaged organelles and pathogens. This catabolic process provides essential cellular building blocks upon nutrient deprivation. Cellular metabolism, especially mitochondrial respiration, has a significant influence on autophagic flux, and complex I function is required for maximal autophagy. In Parkinson’s disease mitochondrial function is frequently impaired and autophagic flux is altered. Thus, dysfunctional organelles and protein aggregates accumulate and cause cellular damage. In order to investigate the interdependency between mitochondrial function and autophagy, novel tool compounds are required. Herein, we report the discovery of a structurally novel autophagy inhibitor (Authipyrin) using a high content screening approach. Target identification and validation led to the discovery that Authipyrin targets mitochondrial complex I directly, leading to the potent inhibition of mitochondrial respiration as well as autophagy.

Place, publisher, year, edition, pages
2019. Vol. 27, no 12, p. 2444-2448
Keywords [en]
Thienopyrimidines, Autophagy, Mitochondrial respiration, Complex I, Inhibitor
National Category
Organic Chemistry Biochemistry and Molecular Biology
Research subject
Biorganic Chemistry
Identifiers
URN: urn:nbn:se:umu:diva-157631DOI: 10.1016/j.bmc.2019.02.028ISI: 000468879400020PubMedID: 30795990Scopus ID: 2-s2.0-85061624990OAI: oai:DiVA.org:umu-157631DiVA, id: diva2:1299234
Funder
EU, European Research Council, 678899Swedish Research Council, 2018-04585Knut and Alice Wallenberg Foundation
Note

Special Issue: SI

Available from: 2019-03-26 Created: 2019-03-26 Last updated: 2019-06-12Bibliographically approved

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The full text will be freely available from 2021-03-31 14:28
Available from 2021-03-31 14:28

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Corkery, DaleWu, Yao-Wen

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CiteExportLink to record
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