Superoxide flashes reveal novel properties of mitochondrial reactive oxygen species excitability in cardiomyocytes

Kaitao Li, Wanrui Zhang, Huaqiang Fang, Wenjun Xie, Jie Liu, Ming Zheng, Xianhua Wang, Wang Wang, Wenchang Tan, Heping Cheng

Research output: Contribution to journalArticle

Abstract

Superoxide flash represents quantal and bursting production of mitochondrial reactive oxygen species (ROS) instigated by transient opening of the mitochondrial permeability transition pore (mPTP). Given their critical role in metabolism, ischemia-reperfusion injury, and apoptosis, characterization of flash properties would be valuable to further mechanistic and physiological studies of this newly discovered mitochondrial phenomenon. Here we developed the flash detector FlashSniper based on segmentation of two-dimensional feature maps extracted from time-lapse confocal image stacks, and on the theory for correcting optical distortion of flash-amplitude histograms. Through large-scale analysis of superoxide flashes in cardiomyocytes, we demonstrated uniform mitochondrial ROS excitability among subsarcolemmal and intermyofibrillar mitochondria, and exponential distribution of intervals between consecutive flash events. Flash ignition displayed three different patterns: an abrupt rise from quiescence (44%), a rise with an exponential foot (27%), or a rise occurring after a pedestal precursor (29%), closely resembling action-potential initiation in excitable cells. However, the optical blurring-corrected amplitudes of superoxide flashes were highly variable, as were their durations, indicating stochastic automaticity of single-mitochondrion ROS excitation. Simultaneous measurement of mitochondrial membrane potential revealed that graded, rather than all-or-none, depolarization mirrored the precursor and the primary peak of the flash. We propose that superoxide flash production is a regenerative process dominated by stochastic, autonomous recruitment of a limited number of units (e.g., mPTPs) in single mitochondria.

Original languageEnglish (US)
Pages (from-to)1011-1021
Number of pages11
JournalBiophysical Journal
Volume102
Issue number5
DOIs
StatePublished - Mar 7 2012
Externally publishedYes

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Cardiac Myocytes
Superoxides
Reactive Oxygen Species
Mitochondria
Stochastic Processes
Mitochondrial Membrane Potential
Reperfusion Injury
Action Potentials
Foot
Apoptosis

ASJC Scopus subject areas

  • Biophysics

Cite this

Superoxide flashes reveal novel properties of mitochondrial reactive oxygen species excitability in cardiomyocytes. / Li, Kaitao; Zhang, Wanrui; Fang, Huaqiang; Xie, Wenjun; Liu, Jie; Zheng, Ming; Wang, Xianhua; Wang, Wang; Tan, Wenchang; Cheng, Heping.

In: Biophysical Journal, Vol. 102, No. 5, 07.03.2012, p. 1011-1021.

Research output: Contribution to journalArticle

Li, K, Zhang, W, Fang, H, Xie, W, Liu, J, Zheng, M, Wang, X, Wang, W, Tan, W & Cheng, H 2012, 'Superoxide flashes reveal novel properties of mitochondrial reactive oxygen species excitability in cardiomyocytes', Biophysical Journal, vol. 102, no. 5, pp. 1011-1021. https://doi.org/10.1016/j.bpj.2012.01.044
Li, Kaitao ; Zhang, Wanrui ; Fang, Huaqiang ; Xie, Wenjun ; Liu, Jie ; Zheng, Ming ; Wang, Xianhua ; Wang, Wang ; Tan, Wenchang ; Cheng, Heping. / Superoxide flashes reveal novel properties of mitochondrial reactive oxygen species excitability in cardiomyocytes. In: Biophysical Journal. 2012 ; Vol. 102, No. 5. pp. 1011-1021.
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