ResearchIn-Press PreviewMetabolism Open Access | 10.1172/jci.insight.170185
1Department of Cell Biology and Molecular Medicine, New Jersey Medical School, Rutgers University, Newark, United States of America
2Vascular Medicine Institute & Cardiology, University of Pittsburgh, Pittsburgh, United States of America
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1Department of Cell Biology and Molecular Medicine, New Jersey Medical School, Rutgers University, Newark, United States of America
2Vascular Medicine Institute & Cardiology, University of Pittsburgh, Pittsburgh, United States of America
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1Department of Cell Biology and Molecular Medicine, New Jersey Medical School, Rutgers University, Newark, United States of America
2Vascular Medicine Institute & Cardiology, University of Pittsburgh, Pittsburgh, United States of America
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1Department of Cell Biology and Molecular Medicine, New Jersey Medical School, Rutgers University, Newark, United States of America
2Vascular Medicine Institute & Cardiology, University of Pittsburgh, Pittsburgh, United States of America
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1Department of Cell Biology and Molecular Medicine, New Jersey Medical School, Rutgers University, Newark, United States of America
2Vascular Medicine Institute & Cardiology, University of Pittsburgh, Pittsburgh, United States of America
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1Department of Cell Biology and Molecular Medicine, New Jersey Medical School, Rutgers University, Newark, United States of America
2Vascular Medicine Institute & Cardiology, University of Pittsburgh, Pittsburgh, United States of America
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1Department of Cell Biology and Molecular Medicine, New Jersey Medical School, Rutgers University, Newark, United States of America
2Vascular Medicine Institute & Cardiology, University of Pittsburgh, Pittsburgh, United States of America
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1Department of Cell Biology and Molecular Medicine, New Jersey Medical School, Rutgers University, Newark, United States of America
2Vascular Medicine Institute & Cardiology, University of Pittsburgh, Pittsburgh, United States of America
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Published April 2, 2024 - More info
Duchenne muscular dystrophy (DMD) is a progressive muscle-wasting disease associated with cardiomyopathy. DMD-cardiomyopathy is characterized by abnormal intracellular Ca2+ homeostasis and mitochondrial dysfunction. We used dystrophin and utrophin null (mdx:utrn–/–) mice in sarcolipin (SLN) heterozygous knockout (sln+/–) background to examine the effect of SLN reduction on mitochondrial function in the dystrophic myocardium. Germline reduction of SLN expression in mdx:utrn–/– mice improved cardiac sarco/endoplasmic reticulum (SR) Ca2+ cycling, reduced cardiac fibrosis, and improved cardiac function. At the cellular level, reducing SLN expression prevented mitochondrial Ca2+ overload, reduced mitochondrial membrane potential loss, and improved mitochondrial function. Transmission electron microscopy of myocardial tissues and proteomic analysis of mitochondria-associated membranes show that reducing SLN expression improved mitochondrial structure and SR-mitochondria interactions in dystrophic cardiac myocytes. These findings indicate that SLN upregulation plays a significant role in the pathogenesis of cardiomyopathy and that reducing SLN expression has clinical implications in the treatment of DMD-cardiomyopathy.