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Acyl-coenzyme A thioesterase 15 (THEM5) is a mitochondrial enzyme that hydrolyzes long-chain acyl-CoA esters, with a notable preference for unsaturated substrates such as linoleoyl-CoA[1][5]. THEM5 plays a vital role in the remodeling of cardiolipin, a phospholipid critical for mitochondrial membrane structure and function. Loss of THEM5 activity disrupts mitochondrial lipid homeostasis, leading to altered organelle morphology, impaired respiration, and the development of fatty liver—especially under high-fat dietary conditions. THEM5 is part of the Hotdog-fold protein family of thioesterases and is highly conserved in its catalytic domain. Its biological significance links mitochondrial lipid metabolism to organelle health and systemic energy balance, implicating it in metabolic diseases such as obesity, diabetes, and related liver dysfunctions[1][3][5].
Hydrolysis of long-chain acyl-CoA esters (especially linoleoyl-CoA) to generate free fatty acids and CoA, thus regulating the availability of substrates for mitochondrial lipid remodeling and metabolism[1][5].
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