In EXOG-depleted cardiomyocytes cell death is marked by a decreased mitochondrial reserve capacity of the electron transport chain

Wardit Tigchelaar,Rudolf A De Boer,Wiek H Van Gilst,Anne Margreet De Jong,Herman H W Silljé

doi:10.1002/icl3.1047

Wardit Tigchelaar, Rudolf A De Boer + Show 3 more

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https://doi.org/10.1002/icl3.1047

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Abstract

In EXOG-depleted cardiomyocytes cell death is marked by a decreased mitochondrial reserve capacity of the electron transport chain

Highlights

Cardiac hypertrophy is the cellular response to increased ventricular wall stress and can be induced by a variety of pathological stimuli like hypertension, valvular disease and myocardial infarction, and by physiological stimuli including endurance exercise and pregnancy [1,2,3]
We have recently shown that exonuclease G-like (EXOG) depletion stimulates mitochondrial respiration and causes reactive oxygen species (ROS)-mediated cardiomyocyte hypertrophy [14]
We show that EXOG is an important gene in cardiomyocytes and that cell death is enhanced in EXOGdepleted cells treated with the pathological stress factor PE

Summary

Introduction

Cardiac hypertrophy is the cellular response to increased ventricular wall stress and can be induced by a variety of pathological stimuli like hypertension, valvular disease and myocardial infarction, and by physiological stimuli including endurance exercise and pregnancy [1,2,3]. Hypertrophy is defined by an increase in cardiomyocyte size and is accompanied by enhanced protein synthesis and changes in sarcomere organization [4] This response is initially an adaptive mechanism of the heart to cope with this increased wall stress. Hypertrophy induced by sustained pathological stimulation, like neurohormonal stimulation, is not reversible and may become maladaptive Under these conditions, the initially adaptive response of compensated hypertrophy may advance into decompensated hypertrophy and subsequently result in heart failure [5]. It is more and more recognized that mitochondrial dysfunction is an important event in the development of heart failure [8] This is plausible, as the heart is the most energy-consuming organ in the body and is largely dependent on mitochondrial metabolism to generate energy in the form of ATP to sustain proper cardiac function [9]. The basic aspects of mitochondrial metabolism and energetics, including electron transfer and ATP production, are well established, relatively little is

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