title: Coordinated behavior of mitochondria in both space and time: a reactive oxygen species-activated wave of mitochondrial depolarization.
abstract: Reactive oxygen species (ROS) can trigger a transient burst of mitochondrial ROS production via ROS activation of the mitochondrial permeability transition pore (MPTP), a phenomenon termed ROS-induced ROS release (RIRR). The goal of this study was to investigate if the generation of ROS in a discrete region of a cardiomyocyte could serve to propagate RIRR-mediated mitochondrial depolarizations throughout a cell. Our experiments revealed that localized RIRR activated either RIRR-mediated fluctuations in mitochondrial membrane potential (time period: 3-10 min) or a traveling wave of depolarization of the cell's mitochondria (velocity: approximately 5 microm/min). Both phenomena appeared to be mediated by the mitochondrial permeability transition pore and eventually encompassed the majority of the mitochondrial population of both isolated rat and rabbit cardiomyocytes. Furthermore, depolarization was often reversible; the waves of depolarization were then followed by a rapid (approximately 40 microm/min) repolarization wave of the mitochondria. We show that the RIRR can function to communicate the mitochondrial permeability transition from one mitochondrion to another in the isolated adult cardiomyocyte.
authors.affiliation: Department of Molecular Cell Physiology, The Centre for Research on BioComplex Systems, BioCentrum Amsterdam, NL-1081 HV, Amsterdam, The Netherlands.
authors.forename: Nathan R
authors.initials: NR
authors.lastname: Brady
authors.forename: Steven P
authors.initials: SP
authors.lastname: Elmore
authors.forename: Johannes J H G M
authors.initials: JJ
authors.lastname: van Beek
authors.forename: Klaas
authors.initials: K
authors.lastname: Krab
authors.forename: Pierre J
authors.initials: PJ
authors.lastname: Courtoy
authors.forename: Louis
authors.initials: L
authors.lastname: Hue
authors.forename: Hans V
authors.initials: HV
authors.lastname: Westerhoff
mesh_terms: D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism; D007091:Image Processing, Computer-Assisted; D007700:Kinetics; D008027:Light; D008564:Membrane Potentials; D018613:Microscopy, Confocal; D008928:Mitochondria / Q000378:metabolism*; D008954:Models, Biological; D032383:Myocytes, Cardiac / Q000378:metabolism*; D011817:Rabbits; D017382:Reactive Oxygen Species; D012402:Rotenone / Q000494:pharmacology; D013997:Time Factors
chemical_list: D017382:Reactive Oxygen Species; D012402:Rotenone; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D002118:Calcium