title: The pharmacological regulation of cellular mitophagy.
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.
authors.affiliation: Department of Comparative Biomedical Sciences, The Royal Veterinary College, University of London, London, UK.|UCL School of Pharmacy, London, UK.
authors.forename: Nikolaos D
authors.initials: ND
authors.lastname: Georgakopoulos
authors.affiliation: UCL School of Pharmacy, London, UK.
authors.forename: Geoff
authors.initials: G
authors.lastname: Wells
authors.affiliation: Department of Comparative Biomedical Sciences, The Royal Veterinary College, University of London, London, UK.|University College London Consortium for Mitochondrial Research, London, UK.
authors.forename: Michelangelo
authors.initials: M
authors.lastname: Campanella
mesh_terms: D000968:Antimycin A / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D063306:Mitophagy / Q000187:drug effects*; D015394:Molecular Structure; D009840:Oligomycins / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D009840:Oligomycins; D000968:Antimycin A