Complex I Deficiency Due to Selective Loss of Ndufs4 in the Mouse Heart Results in Severe Hypertrophic Cardiomyopathy

Overview

Journal PLoS One

Specialties General Medicine
Science

Date 2014 Apr 8

PMID 24705922

Citations 26

Authors

Edward T Chouchani

Carmen Methner

Guido Buonincontri

Chou-Hui Hu

Angela Logan

Stephen J Sawiak

Michael P Murphy

Thomas Krieg

Affiliations

Soon will be listed here.

Abstract

Mitochondrial complex I, the primary entry point for electrons into the mitochondrial respiratory chain, is both critical for aerobic respiration and a major source of reactive oxygen species. In the heart, chronic dysfunction driving cardiomyopathy is frequently associated with decreased complex I activity, from both genetic and environmental causes. To examine the functional relationship between complex I disruption and cardiac dysfunction we used an established mouse model of mild and chronic complex I inhibition through heart-specific Ndufs4 gene ablation. Heart-specific Ndufs4-null mice had a decrease of ∼ 50% in complex I activity within the heart, and developed severe hypertrophic cardiomyopathy as assessed by magnetic resonance imaging. The decrease in complex I activity, and associated cardiac dysfunction, occurred absent an increase in mitochondrial hydrogen peroxide levels in vivo, accumulation of markers of oxidative damage, induction of apoptosis, or tissue fibrosis. Taken together, these results indicate that diminished complex I activity in the heart alone is sufficient to drive hypertrophic cardiomyopathy independently of alterations in levels of mitochondrial hydrogen peroxide or oxidative damage.

Citing Articles

Genetic Mutations and Mitochondrial Redox Signaling as Modulating Factors in Hypertrophic Cardiomyopathy: A Scoping Review.

Junior A, Franca-E-Silva A, de Oliveira H, de Lima K, Porto I, Pedroso T Int J Mol Sci. 2024; 25(11).

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Structural insights into respiratory complex I deficiency and assembly from the mitochondrial disease-related ndufs4 mouse.

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