Journal
SCIENTIFIC REPORTS
Volume 10, Issue 1, Pages -Publisher
NATURE RESEARCH
DOI: 10.1038/s41598-020-71308-z
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Funding
- NHLBI NIH HHS [R01 HL126802, R01 HL137259, R01 HL134821, R01 HL142496] Funding Source: Medline
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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.
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