Etfa, also known as electron transfer flavoprotein subunit alpha, is involved in multiple important biological processes. It plays a key role in fatty acid, amino acid, and choline metabolism as part of the electron transfer flavoprotein (ETF) complex, which is crucial for the function of mitochondrial dehydrogenases in these metabolic pathways [1,2].

In a study on multiple acyl-CoA dehydrogenase deficiency (MADD), a novel homozygous promoter variant in Etfa (c.-85G > A) was identified in a patient with MADD. This variant led to decreased Etfa protein expression in lymphoblasts and reduced promoter activity, suggesting a potential late-onset form of MADD (Type III). This finding helps in understanding the genetic etiology of MADD and establishing a molecular diagnosis in similar patients [1].

In another study, the Acox2 -/- mouse model showed that non-histone lysine crotonylation (Kcr) levels were downregulated in the liver, and 54% of downregulated non-histone Kcr sites were in mitochondrial and peroxisomal enzymes including Etfa. This indicates a role of Etfa in the context of Kcr-mediated hepatic metabolic homeostasis [2].

In conclusion, Etfa is essential for normal metabolism of fatty acids, amino acids, and choline. Studies on genetic variants and animal models like the Acox2 -/- mice have revealed its significance in metabolic disorders such as MADD and hepatic metabolic homeostasis. Understanding Etfa's function can provide insights into the mechanisms of these diseases and potentially lead to new diagnostic and treatment strategies.

References:

1. Prasun, Pankaj, Evans, Anthony, Cork, Emalyn, Houten, Sander M, Webb, Bryn D. 2022. A novel deleterious ETFA promoter variant causative of multiple acyl-CoA dehydrogenase deficiency. In American journal of medical genetics. Part A, 191, 1089-1093. doi:10.1002/ajmg.a.63104. https://pubmed.ncbi.nlm.nih.gov/36579410/

2. Zhang, Yuan, Chen, Yuling, Zhang, Zhao, Zhao, Jianyuan, Zhou, Xiangyu. 2022. Acox2 is a regulator of lysine crotonylation that mediates hepatic metabolic homeostasis in mice. In Cell death & disease, 13, 279. doi:10.1038/s41419-022-04725-9. https://pubmed.ncbi.nlm.nih.gov/35351852/