New research reveals how estrogen-related receptors influence muscle fatigue recovery, offering fresh insights into potential treatments for metabolic disorders.
Published in the Proceedings of the National Academy of Sciences (PNAS), the study highlights the crucial role of estrogen-related receptors (ERRs) in regulating energy metabolism. This discovery could reshape our understanding of cellular function.
Mitochondria, often called the cell’s powerhouses, are essential for energy production. When these organelles malfunction, it can lead to severe conditions such as cancer, multiple sclerosis, heart disease, dementia, and age-related metabolic decline. One in 5,000 people is affected by mitochondrial disorders.
Unlike classical estrogen receptors, which bind directly to estrogen, ERRs operate differently. They regulate various cellular signaling pathways and are vital in metabolic processes, even without binding to estrogen.
“This study is among the first to recognize the pivotal role of estrogen-related receptors in energy metabolism—an area that has remained largely unexplored,” said lead researcher Professor Ronald Evans.
The team investigated this by removing three types of ERRs—alpha, beta, and gamma—from mice’s muscle tissue to observe the effects.
Interestingly, eliminating alpha receptors had a minimal effect, as they comprise only 4% of the ERR population in muscle tissue. However, gamma receptors stepped in to compensate for the loss under normal conditions, revealing an adaptive mechanism previously unknown to scientists.
The study also emphasizes the role of PGC1α, a protein that promotes mitochondrial development and function. Although PGC1α cannot directly bind to DNA like nuclear hormone receptors, it relies on partner proteins—such as ERRs—to exert its effects. PGC1α is considered a key co-activator for ERRs.
The findings suggest that ERRs are central to energy metabolism and muscle fatigue recovery, potentially paving the way for new, targeted treatments for metabolic diseases.
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