title: Imaging superoxide flash and metabolism-coupled mitochondrial permeability transition in living animals.
abstract: The mitochondrion is essential for energy metabolism and production of reactive oxygen species (ROS). In intact cells, respiratory mitochondria exhibit spontaneous "superoxide flashes", the quantal ROS-producing events consequential to transient mitochondrial permeability transition (tMPT). Here we perform the first in vivo imaging of mitochondrial superoxide flashes and tMPT activity in living mice expressing the superoxide biosensor mt-cpYFP, and demonstrate their coupling to whole-body glucose metabolism. Robust tMPT/superoxide flash activity occurred in skeletal muscle and sciatic nerve of anesthetized transgenic mice. In skeletal muscle, imaging tMPT/superoxide flashes revealed labyrinthine three-dimensional networks of mitochondria that operate synchronously. The tMPT/superoxide flash activity surged in response to systemic glucose challenge or insulin stimulation, in an apparently frequency-modulated manner and involving also a shift in the gating mode of tMPT. Thus, in vivo imaging of tMPT-dependent mitochondrial ROS signals and the discovery of the metabolism-tMPT-superoxide flash coupling mark important technological and conceptual advances for the study of mitochondrial function and ROS signaling in health and disease.
authors.affiliation: Institute of Molecular Medicine, College of Life Science, Peking University, Beijing 100871, China.
authors.forename: Huaqiang
authors.initials: H
authors.lastname: Fang
authors.forename: Min
authors.initials: M
authors.lastname: Chen
authors.forename: Yi
authors.initials: Y
authors.lastname: Ding
authors.forename: Wei
authors.initials: W
authors.lastname: Shang
authors.forename: Jiejia
authors.initials: J
authors.lastname: Xu
authors.forename: Xing
authors.initials: X
authors.lastname: Zhang
authors.forename: Wanrui
authors.initials: W
authors.lastname: Zhang
authors.forename: Kaitao
authors.initials: K
authors.lastname: Li
authors.forename: Yao
authors.initials: Y
authors.lastname: Xiao
authors.forename: Feng
authors.initials: F
authors.lastname: Gao
authors.forename: Shujiang
authors.initials: S
authors.lastname: Shang
authors.forename: Jing-Chao
authors.initials: JC
authors.lastname: Li
authors.forename: Xiao-Li
authors.initials: XL
authors.lastname: Tian
authors.forename: Shi-Qiang
authors.initials: SQ
authors.lastname: Wang
authors.forename: Jingsong
authors.initials: J
authors.lastname: Zhou
authors.forename: Noah
authors.initials: N
authors.lastname: Weisleder
authors.forename: Jianjie
authors.initials: J
authors.lastname: Ma
authors.forename: Kunfu
authors.initials: K
authors.lastname: Ouyang
authors.forename: Ju
authors.initials: J
authors.lastname: Chen
authors.forename: Xianhua
authors.initials: X
authors.lastname: Wang
authors.forename: Ming
authors.initials: M
authors.lastname: Zheng
authors.forename: Wang
authors.initials: W
authors.lastname: Wang
authors.forename: Xiuqin
authors.initials: X
authors.lastname: Zhang
authors.forename: Heping
authors.initials: H
authors.lastname: Cheng
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D004734:Energy Metabolism; D005947:Glucose / Q000378:metabolism; D007328:Insulin / Q000378:metabolism; D008164:Luminescent Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D018613:Microscopy, Confocal; D008928:Mitochondria / Q000378:metabolism*; D033681:Mitochondrial Membrane Transport Proteins / Q000378:metabolism*; D000083162:Mitochondrial Permeability Transition Pore; D018482:Muscle, Skeletal / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction; D013481:Superoxides / Q000378:metabolism*
chemical_list: D001426:Bacterial Proteins; D007328:Insulin; D008164:Luminescent Proteins; D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D017382:Reactive Oxygen Species; C054562:yellow fluorescent protein, Bacteria; D013481:Superoxides; D005947:Glucose