title: Superoxide flashes: elemental events of mitochondrial ROS signaling in the heart.
abstract: The role of mitochondrial reactive oxygen species (mitoROS) in cellular function remains obscure. By synthesizing recent data, we propose here that local dynamic mitoROS in the form of "superoxide flashes" serve as "signaling ROS" rather than "homeostatic ROS", distinguishable from basal mitoROS due to constitutive leakage of the electron transfer chain (ETC). Individual superoxide flashes are 10-s mitoROS bursts that are compartmentalized to a single mitochondrion or local mitochondrial networks. As a highly-conserved universal mitochondrial activity, it occurs in intact cells, in ex vivo beating hearts, and even in living animals. Unlike basal mitoROS, superoxide flashes are ignited by transient openings of a type of mitochondrial permeability transition pore (mPTP), and their incidence is richly regulated by an array of factors that converge on either the mPTP or ETC. Emerging evidence has shown that superoxide flashes decode dietary and metabolic status or exercise, gauge oxidative stress (e.g., during reoxygenation after hypoxia or anoxia), and constitute early mitochondrial signals that initiate oxidative stress-related apoptosis in a context-dependent manner. That they make only a miniscule contribution to global ROS attests to the high efficiency of local ROS signaling. However, the exact mechanisms underlying superoxide flash formation, regulation and function remain uncertain. Future investigation is warranted to uncover the cellular logic and molecular pathways of local dynamic mitoROS signaling in heart muscle cells and many other cell types.
authors.affiliation: Institute of Molecular Medicine and State Key Laboratory of Biomembrane and Membrane Biotechnology, Peking-Tsinghua Center for Life Sciences, Peking University, Beijing 100871, China.
authors.forename: Xianhua
authors.initials: X
authors.lastname: Wang
authors.forename: Chongshu
authors.initials: C
authors.lastname: Jian
authors.forename: Xing
authors.initials: X
authors.lastname: Zhang
authors.forename: Zhanglong
authors.initials: Z
authors.lastname: Huang
authors.forename: Jiejia
authors.initials: J
authors.lastname: Xu
authors.forename: Tingting
authors.initials: T
authors.lastname: Hou
authors.forename: Wei
authors.initials: W
authors.lastname: Shang
authors.forename: Yi
authors.initials: Y
authors.lastname: Ding
authors.forename: Wanrui
authors.initials: W
authors.lastname: Zhang
authors.forename: Meng
authors.initials: M
authors.lastname: Ouyang
authors.forename: Yuefan
authors.initials: Y
authors.lastname: Wang
authors.forename: Zhen
authors.initials: Z
authors.lastname: Yang
authors.forename: Ming
authors.initials: M
authors.lastname: Zheng
authors.forename: Heping
authors.initials: H
authors.lastname: Cheng
mesh_terms: D000818:Animals; D004579:Electron Transport; D006706:Homeostasis; D006801:Humans; D008929:Mitochondria, Heart / Q000378:metabolism*; D033681:Mitochondrial Membrane Transport Proteins / Q000378:metabolism / Q000502:physiology; D000083162:Mitochondrial Permeability Transition Pore; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D010084:Oxidation-Reduction; D015398:Signal Transduction; D013481:Superoxides / Q000378:metabolism*
chemical_list: D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D013481:Superoxides