COUP-TFII Gene Found to Promote Mitochondrial Dysfunction and Heart Failure

COUP-TFII Gene Found to Promote Mitochondrial Dysfunction and Heart Failure

A new study led by researchers at Baylor College of Medicine in Houston, Texas recently revealed that a gene called COUP-TFII can promote mitochondrial dysfunction and ultimately lead to cardiomyopathy and heart failure. The study was published in the journal Nature Communications and is entitled “Increased COUP-TFII expression in adult hearts induces mitochondrial dysfunction resulting in heart failure.

Cardiomyopathy, a condition characterized by a malfunction of the heart muscle, is known to be linked to metabolic remodeling and dysfunction of mitochondria, the cell’s organelles responsible for energy production.

In the study, researchers found that the gene COUP-TFII, which is known to play a key role during heart development, is involved in the pathogenesis of dilated cardiomyopathy when it is overexpressed. The team found that in mice, overexpression of COUP-TFII promotes heart failure.

“We knew that in heart failure patients there is an overexpression of the gene COUP-TFII,” said the study’s co-senior author Dr. Sophia Tsai in a news release. “Using mouse models with overexpression of COUP-TFII with a similar level of what we observed in patients, we saw a rapid decline in health. So we looked into why this happens.”

The team found that COUP-TFII influences mitochondrial gene expression by controlling genes important for a proper mitochondrial function, dynamics and oxidative stress detoxification. The overexpression of COUP-TFII results in high levels of reactive oxygen species, a natural byproduct of the mitochondria which can damage cells and tissues potentially leading to heart failure.

“When the system functions properly, COUP-TFII expression is very low. But when its expression is induced in heart disease patients, the mitochondria function is disrupted, which damages the heart,” explained the study’s co-senior author Dr. Ming-Jer Tsai. “So we found that if we suppress this gene in mouse models we could prolong life.”


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The research team concluded that COUP-TFII influences mitochondrial function and plays a key role in dilated cardiomyopathy. Based on animal studies, the authors suggest that therapies targeting COUP-TFII could potentially attenuate cardiac dilation, improving the survival rate of patients suffering from dilated cardiomyopathy.

“It was thought that the gene expression was a consequence of dilated cardiomyopathy, but we have found that it is part of the cause,” concluded Dr. Ming-Jer Tsai. “This gives us a target for further research needed before clinical application.” The team’s next goal is to find a proper inhibitor for COUP-TFII.

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