Hydrogen peroxide diffusion and scavenging shapes mitochondrial network instability and failure by sensitizing ROS-induced ROS release
Year: 2020
Type: article
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.
Source: Scientific Reports
Institutions: Johns Hopkins University, Johns Hopkins Medicine
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $1,870
Awards: Exploration of Arrhythmogenic Triggers and Substrates in Heart Failure, Molecular Determinants of Mitochondrial Instability and Arrhythmias, Infarct-related Ventricular Tachycardia Mechanisms: From Micro to Clinical, Targeting Metabo-Redox Network Vulnerability in Heart Failure and Sudden Death
OpenAlex ID: W3087866663