title: Toward high-content screening of mitochondrial morphology and membrane potential in living cells.
abstract: Mitochondria are double membrane organelles involved in various key cellular processes. Governed by dedicated protein machinery, mitochondria move and continuously fuse and divide. These "mitochondrial dynamics" are bi-directionally linked to mitochondrial and cell functional state in space and time. Due to the action of the electron transport chain (ETC), the mitochondrial inner membrane displays a inside-negative membrane potential (Δψ). The latter is considered a functional readout of mitochondrial "health" and required to sustain normal mitochondrial ATP production and mitochondrial fusion. During the last decade, live-cell microscopy strategies were developed for simultaneous quantification of Δψ and mitochondrial morphology. This revealed that ETC dysfunction, changes in Δψ and aberrations in mitochondrial structure often occur in parallel, suggesting they are linked potential targets for therapeutic intervention. Here we discuss how combining high-content and high-throughput strategies can be used for analysis of genetic and/or drug-induced effects at the level of individual organelles, cells and cell populations. This article is part of a Directed Issue entitled: Energy Metabolism Disorders and Therapies.
authors: Khondrion BV, Nijmegen, The Netherlands.
authors: Eligio F
authors: EF
authors: Iannetti
authors: Khondrion BV, Nijmegen, The Netherlands; Department of Biochemistry, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, The Netherlands.
authors: Peter H G M
authors: PH
authors: Willems
authors: Khondrion BV, Nijmegen, The Netherlands.
authors: Mina
authors: M
authors: Pellegrini
authors: Khondrion BV, Nijmegen, The Netherlands.
authors: Julien
authors: J
authors: Beyrath
authors: Khondrion BV, Nijmegen, The Netherlands; Department of Pediatrics, Nijmegen Center for Mitochondria disorders, Radboud University Medical Center, Nijmegen, The Netherlands.
authors: Jan A M
authors: JA
authors: Smeitink
authors: Khondrion BV, Nijmegen, The Netherlands.
authors: Lionel
authors: L
authors: Blanchet
authors: Khondrion BV, Nijmegen, The Netherlands; Department of Biochemistry, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, The Netherlands. Electronic address: Werner.Koopman@radboudumc.nl.
authors: Werner J H
authors: WJ
authors: Koopman
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D045222:Electron Transport Chain Complex Proteins / Q000378:metabolism; D004734:Energy Metabolism; D006801:Humans; D053078:Membrane Potential, Mitochondrial; D008928:Mitochondria / Q000235:genetics* / Q000378:metabolism / Q000648:ultrastructure; D051336:Mitochondrial Membranes / Q000378:metabolism* / Q000648:ultrastructure; D010084:Oxidation-Reduction
chemical_list: D045222:Electron Transport Chain Complex Proteins; D000255:Adenosine Triphosphate
keywords: Data mining; Machine learning; Mitochondrial pathophysiology; Multivariate analysis; TMRM