Imaging superoxide flash and metabolism-coupled mitochondrial permeability transition in living animals |
| |
Authors: | Fang Huaqiang Chen Min Ding Yi Shang Wei Xu Jiejia Zhang Xing Zhang Wanrui Li Kaitao Xiao Yao Gao Feng Shang Shujiang Li Jing-Chao Tian Xiao-Li Wang Shi-Qiang Zhou Jingsong Weisleder Noah Ma Jianjie Ouyang Kunfu Chen Ju Wang Xianhua Zheng Ming Wang Wang Zhang Xiuqin Cheng Heping |
| |
Affiliation: | Institute of Molecular Medicine, College of Life Science, Peking University, Beijing 100871, China. |
| |
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. |
| |
Keywords: | reactive oxygen species mitochondrial permeability transition energy metabolism in vivo molecular imaging |
本文献已被 PubMed 等数据库收录! |
|