Regulation of superoxide flashes by transient and steady mitochondrial calcium elevations  

作　　者：JIAN ChongShu HOU TingTing YIN RongKang CHENG HePing WANG XianHua 

机构地区：[1]State Key Laboratory of Biomembrane and Membrane Biotechnology,Beijing Key Laboratory of Cardiometabolic Molecular Medicine,Institute of Molecular Medicine,Peking-Tsinghua Center for Life Sciences,Peking University

出　　处：《Science China(Life Sciences)》2014年第5期495-501,共7页中国科学（生命科学英文版）

基　　金：supported by the National Key Basic Research Program of China(2011CB809100,2013CB531200);the National Natural Science Foundation of China(31221002,31130067,31123004,30900264)

摘　　要：The mitochondria play essential roles in both intracellular calcium and reactive oxygen species signaling.As a newly discovered universal and fundamental mitochondrial phenomenon,superoxide flashes reflect transient bursts of superoxide production in the matrix of single mitochondria.Whether and how the superoxide flash activity is regulated by mitochondrial calcium remain largely unknown.Here we demonstrate that elevating mitochondrial calcium either by the calcium ionophore ionomycin or by increasing the bathing calcium in permeabilized HeLa cells increases superoxide flash incidence,and inhibition of the mitochondrial calcium uniporter activity abolishes the flash response.Quantitatively,the superoxide flash incidence is correlated to the steady-state mitochondrial calcium elevation with 1.7-fold increase per 1.0?F/F0 of Rhod-2 signal.In contrast,large mitochondrial calcium transients(e.g.,peak△F/F0~2.8,duration^2 min)in the absence of steady-state elevations failed to alter the flash activity.These results indicate that physiological levels of sustained,but not transient,mitochondrial calcium elevation acts as a potent regulator of superoxide flashes,but its mechanism of action likely involves a multi-step,slow-onset process.The mitochondria play essential roles in both intracellular calcium and reactive oxygen species signaling.As a newly discovered universal and fundamental mitochondrial phenomenon,superoxide flashes reflect transient bursts of superoxide production in the matrix of single mitochondria.Whether and how the superoxide flash activity is regulated by mitochondrial calcium remain largely unknown.Here we demonstrate that elevating mitochondrial calcium either by the calcium ionophore ionomycin or by increasing the bathing calcium in permeabilized HeLa cells increases superoxide flash incidence,and inhibition of the mitochondrial calcium uniporter activity abolishes the flash response.Quantitatively,the superoxide flash incidence is correlated to the steady-state mitochondrial calcium elevation with 1.7-fold increase per 1.0？F/F0 of Rhod-2 signal.In contrast,large mitochondrial calcium transients（e.g.,peak△F/F0-2.8,duration-2 min）in the absence of steady-state elevations failed to alter the flash activity.These results indicate that physiological levels of sustained,but not transient,mitochondrial calcium elevation acts as a potent regulator of superoxide flashes,but its mechanism of action likely involves a multi-step,slow-onset process.

关 键 词：superoxide flash calcium signaling reactive oxygen species （ROS） MITOCHONDRION 

分 类 号：Q25[生物学—细胞生物学]