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

Brent Millare, Brian O’Rourke, Natalia Trayanova

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish (US)
Article number15758
JournalScientific reports
Volume10
Issue number1
DOIs
StatePublished - Dec 1 2020

ASJC Scopus subject areas

  • General

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