title: A wave of reactive oxygen species (ROS)-induced ROS release in a sea of excitable mitochondria.
abstract: Once considered simply as the main source of ATP, mitochondria are now implicated in the control of many additional aspects of cell physiology, such as calcium signaling, and pathology, as in injury incurred on ischemia and subsequent reperfusion (I/R). Mitochondrial respiration is ordinarily accompanied by low-level ROS production, but they can respond to elevated ROS concentrations by increasing their own ROS production, a phenomenon termed ROS-induced ROS release (RIRR). Two modes of RIRR have been described. In the first mode of RIRR, enhanced ROS leads to mitochondrial depolarization via activation of the MPTP, yielding a short-lived burst of ROS originating from the mitochondrial electron transport chain (ETC). The second mode of RIRR is MPTP independent but is regulated by the mitochondrial benzodiazepine receptor (mBzR). Increased ROS in the mitochondrion triggers opening of the inner mitochondrial membrane anion channel (IMAC), resulting in a brief increase in ETC-derived ROS. Both modes of RIRR have been shown to transmit localized mitochondrial perturbations throughout the cardiac cell in the form of oscillations or waves but are kinetically distinct and may involve different ROS that serve as second messengers. In this review, we discuss the mechanisms of these different modes of RIRR.
authors.affiliation: Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, California 92037, USA.
authors.forename: Nathan R
authors.initials: NR
authors.lastname: Brady
authors.forename: Anne
authors.initials: A
authors.lastname: Hamacher-Brady
authors.forename: Hans V
authors.initials: HV
authors.lastname: Westerhoff
authors.forename: Roberta A
authors.initials: RA
authors.lastname: Gottlieb
mesh_terms: D000818:Animals; D006801:Humans; D008564:Membrane Potentials / Q000502:physiology; D008928:Mitochondria / Q000378:metabolism* / Q000502:physiology*; D033681:Mitochondrial Membrane Transport Proteins / Q000502:physiology; D000083162:Mitochondrial Permeability Transition Pore; D008954:Models, Biological; D017382:Reactive Oxygen Species / Q000378:metabolism*; D011963:Receptors, GABA-A / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology; D050994:Voltage-Dependent Anion Channels / Q000502:physiology
chemical_list: D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D017382:Reactive Oxygen Species; D011963:Receptors, GABA-A; D050994:Voltage-Dependent Anion Channels