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Estrogen Related Receptor Alpha (ERRα) also known as NR3B1 is an orphan nuclear receptor with a molecular mass of approximately 51 kDa. It acts as a transcription factor and influences the expression of genes involved in energy metabolism. ERRα is expressed in numerous tissues such as the liver heart kidney and skeletal muscles. It binds to DNA as a monomer and alters specific gene expression activities. This protein lacks an identified ligand which classifies it as an orphan receptor but it shares structural similarities with estrogen receptors allowing the regulation of gene transcription in several physiological contexts.

Biological function summary

Estrogen Related Receptor Alpha regulates cellular energy production processes including mitochondrial biogenesis and oxidative phosphorylation. It plays a role in the biological function of energy homeostasis and increases the expression of genes related to metabolic processes. ERRα operates as part of a transcriptional regulatory network and interacts with other nuclear receptors and coactivators to modulate its activity. It often forms complexes with coactivators such as peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) to exert its effects on mitochondrial function.

Pathways

ERRα is integral to the PGC-1α signaling pathway and the AMPK (AMP-activated protein kinase) signaling pathway. These pathways are important in regulating energy metabolism and adaptive thermogenesis. ERRα interacts with PGC-1α to enhance mitochondrial function and energy expenditure while AMPK activation affects ERRα transcriptional activity and facilitates cellular energy balance. Additionally ERRα cross-talks with other nuclear receptors like PPAR (peroxisome proliferator-activated receptor) family members which are involved in lipid metabolism and glucose homeostasis.

ERRα has implications in metabolic conditions such as diabetes and obesity. The protein links to diabetes through its role in mitochondrial dysfunction and insulin resistance. Obesity-related studies point out how ERRα affects adaptive thermogenesis and lipid metabolism contributing to energy imbalance. ERRα-PPAR interactions highlight its association in metabolic disorders influencing various aspects of metabolism and disease progression. Understanding ERRα function offers therapeutic potential for targeting metabolic diseases.