4.7 Article

Hydrogen peroxide diffusion and scavenging shapes mitochondrial network instability and failure by sensitizing ROS-induced ROS release

期刊

SCIENTIFIC REPORTS
卷 10, 期 1, 页码 -

出版社

NATURE RESEARCH
DOI: 10.1038/s41598-020-71308-z

关键词

-

资金

  1. NHLBI NIH HHS [R01 HL126802, R01 HL137259, R01 HL134821, R01 HL142496] Funding Source: Medline

向作者/读者索取更多资源

The mitochondrial network of cardiac cells is finely tuned for ATP delivery to sites of energy demand; however, emergent phenomena, such as mitochondrial transmembrane potential oscillations or propagating waves of depolarization have been observed under metabolic stress. While regenerative signaling by reactive oxygen species (ROS)-induced ROS release (RIRR) has been suggested as a potential trigger, it is unknown how it could lead to widespread responses. Here, we present a novel computational model of RIRR transmission that explains the mechanisms of this phenomenon. The results reveal that superoxide mediates neighbor-neighbor activation of energy-dissipating ion channels, while hydrogen peroxide distributes oxidative stress to sensitize the network to mitochondrial criticality. The findings demonstrate the feasibility of RIRR as a synchronizing factor across the dimensions of the adult heart cell and illustrate how a cascade of failures at the organellar level can scale to impact cell and organ level functions of the heart.

作者

我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。

评论

主要评分

4.7
评分不足

次要评分

新颖性
-
重要性
-
科学严谨性
-
评价这篇论文

推荐

暂无数据
暂无数据