title: Mitochondrial Flash: Integrative Reactive Oxygen Species and pH Signals in Cell and Organelle Biology.
abstract: Recent breakthroughs in mitochondrial research have advanced, reshaped, and revolutionized our view of the role of mitochondria in health and disease. These discoveries include the development of novel tools to probe mitochondrial biology, the molecular identification of mitochondrial functional proteins, and the emergence of new concepts and mechanisms in mitochondrial function regulation. The discovery of "mitochondrial flash" activity has provided unique insights not only into real-time visualization of individual mitochondrial redox and pH dynamics in live cells but has also advanced understanding of the excitability, autonomy, and integration of mitochondrial function in vivo.
  
  
  
  The mitochondrial flash is a transient and stochastic event confined within an individual mitochondrion and is observed in a wide range of organisms from plants to Caenorhabditis elegans to mammals. As flash events involve multiple transient concurrent changes within the mitochondrion (e.g., superoxide, pH, and membrane potential), a number of different mitochondrial targeted fluorescent indicators can detect flash activity. Accumulating evidence indicates that flash events reflect integrated snapshots of an intermittent mitochondrial process arising from mitochondrial respiration chain activity associated with the transient opening of the mitochondrial permeability transition pore.
  
  
  
  We review the history of flash discovery, summarize current understanding of flash biology, highlight controversies regarding the relative roles of superoxide and pH signals during a flash event, and bring forth the integration of both signals in flash genesis.
  
  
  
  Investigations using flash as a biomarker and establishing its role in cell signaling pathway will move the field forward. Antioxid. Redox Signal. 25, 534-549.
authors.affiliation: 1 Department of Anesthesiology and Pain Medicine, Mitochondria and Metabolism Center, University of Washington , Seattle, Washington.
authors.forename: Wang
authors.initials: W
authors.lastname: Wang
authors.affiliation: 1 Department of Anesthesiology and Pain Medicine, Mitochondria and Metabolism Center, University of Washington , Seattle, Washington.
authors.forename: Guohua
authors.initials: G
authors.lastname: Gong
authors.affiliation: 2 State Key Laboratory of Membrane Biology, Institute of Molecular Medicine, Peking-Tsinghua Center for Life Sciences, Peking University , Beijing, China .
authors.forename: Xianhua
authors.initials: X
authors.lastname: Wang
authors.affiliation: 3 Department of Pharmacology and Physiology, University of Rochester Medical Center , Rochester, New York.
authors.forename: Lan
authors.initials: L
authors.lastname: Wei-LaPierre
authors.affiliation: 2 State Key Laboratory of Membrane Biology, Institute of Molecular Medicine, Peking-Tsinghua Center for Life Sciences, Peking University , Beijing, China .
authors.forename: Heping
authors.initials: H
authors.lastname: Cheng
authors.affiliation: 3 Department of Pharmacology and Physiology, University of Rochester Medical Center , Rochester, New York.
authors.forename: Robert
authors.initials: R
authors.lastname: Dirksen
authors.affiliation: 4 Department of Medicine, Center for Translational Medicine, Sidney Kimmel Medical College, Thomas Jefferson University , Philadelphia, Pennsylvania.
authors.forename: Shey-Shing
authors.initials: SS
authors.lastname: Sheu
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D015415:Biomarkers; D015374:Biosensing Techniques; D002468:Cell Physiological Phenomena; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008164:Luminescent Proteins / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism*; D010084:Oxidation-Reduction; D010085:Oxidative Phosphorylation; D017382:Reactive Oxygen Species / Q000378:metabolism*; D015398:Signal Transduction; D013481:Superoxides / Q000378:metabolism
chemical_list: D000975:Antioxidants; D015415:Biomarkers; D008164:Luminescent Proteins; D017382:Reactive Oxygen Species; D013481:Superoxides