Imaging superoxide flash and metabolism-coupled mitochondrial permeability transition in living animals

Huaqiang Fang, Min Chen, Yi Ding, Wei Shang, Jiejia Xu, Xing Zhang, Wanrui Zhang, Kaitao Li, Yao Xiao, Feng Gao, Shujiang Shang, Jing Chao Li, Xiao Li Tian, Shi Qiang Wang, Jingsong Zhou, Noah Weisleder, Jianjie Ma, Kunfu Ouyang, Ju Chen, Xianhua WangMing Zheng, Wang Wang, Xiuqin Zhang, Heping Cheng

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)1295-1304
Number of pages10
JournalCell Research
Volume21
Issue number9
DOIs
StatePublished - Sep 1 2011
Externally publishedYes

Keywords

  • energy metabolism
  • in vivo molecular imaging
  • mitochondrial permeability transition
  • reactive oxygen species

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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  • Cite this

    Fang, H., Chen, M., Ding, Y., Shang, W., Xu, J., Zhang, X., Zhang, W., Li, K., Xiao, Y., Gao, F., Shang, S., Li, J. C., Tian, X. L., Wang, S. Q., Zhou, J., Weisleder, N., Ma, J., Ouyang, K., Chen, J., ... Cheng, H. (2011). Imaging superoxide flash and metabolism-coupled mitochondrial permeability transition in living animals. Cell Research, 21(9), 1295-1304. https://doi.org/10.1038/cr.2011.81