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The pharmacological regulation of cellular mitophagy

Georgakopoulos, ND; Wells, G; Campanella, M; (2017) The pharmacological regulation of cellular mitophagy. Nature Chemical Biology , 13 (2) pp. 136-146. 10.1038/nchembio.2287. Green open access

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Abstract

Small molecules are pharmacological tools of considerable value for dissecting complex biological processes and identifying potential therapeutic interventions. Recently, the cellular quality-control process of mitophagy has attracted considerable research interest; however, the limited availability of suitable chemical probes has restricted our understanding of the molecular mechanisms involved. Current approaches to initiate mitophagy include acute dissipation of the mitochondrial membrane potential (ΔΨm) by mitochondrial uncouplers (for example, FCCP/CCCP) and the use of antimycin A and oligomycin to impair respiration. Both approaches impair mitochondrial homeostasis and therefore limit the scope for dissection of subtle, bioenergy-related regulatory phenomena. Recently, novel mitophagy activators acting independently of the respiration collapse have been reported, offering new opportunities to understand the process and potential for therapeutic exploitation. We have summarized the current status of mitophagy modulators and analyzed the available chemical tools, commenting on their advantages, limitations and current applications.

Type: Article
Title: The pharmacological regulation of cellular mitophagy
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1038/nchembio.2287
Publisher version: http://dx.doi.org/10.1038/nchembio.2287
Language: English
Additional information: Copyright © 2016 Macmillan Publishers Limited, part of Springer Nature. All rights reserved.
Keywords: Cell biology, Metabolism, Neurodegenerative diseases, Small molecules
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > UCL School of Pharmacy
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > UCL School of Pharmacy > SoP Pharmaceutical and Bio Chemistry
URI: https://discovery.ucl.ac.uk/id/eprint/1537663
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