{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n Human HTD2 is a mitochondrial enzyme that plays a key role in the mitochondrial fatty acid synthesis (mtFAS) pathway. HTD2 functions as a 3‐hydroxyacyl–thioester dehydratase, catalyzing a specific dehydration step essential for the elongation of fatty acids within mitochondria. Its enzymatic activity is critical for the production of lipoic acid—a key cofactor required for the proper function of several mitochondrial enzyme complexes such as complex I. In adipocytes, downregulation of HTD2 is associated with impaired mitochondrial complex I activity, elevated oxidative stress, and reduced insulin sensitivity; notably, supplementation with lipoic acid can mitigate these metabolic impairments (refer to."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " Moreover, HTD2 is encoded through a conserved bicistronic gene arrangement together with the RPP14 subunit of RNase P. This genomic organization, which is maintained across vertebrates from fish to humans, underscores a long‐term evolutionary link between RNA processing and mitochondrial fatty acid metabolism (see."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n In summary, HTD2 is essential for mitochondrial lipid metabolism by facilitating a key dehydration reaction in the mtFAS pathway. Through its role in lipoic acid synthesis, HTD2 helps maintain mitochondrial function and energy homeostasis, implicating it in the regulation of cellular metabolic processes and insulin sensitivity.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Mengqi Zeng, Jie Xu, Zhengyi Zhang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Htd2 deficiency-associated suppression of α-lipoic acid production provokes mitochondrial dysfunction and insulin resistance in adipocytes."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Redox Biol (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.redox.2021.101948"}], "href": "https://doi.org/10.1016/j.redox.2021.101948"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33774475"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33774475"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Kaija J Autio, Alexander J Kastaniotis, Helmut Pospiech, et al. "}, {"type": "b", "children": [{"type": "t", "text": "An ancient genetic link between vertebrate mitochondrial fatty acid synthesis and RNA processing."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "FASEB J (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1096/fj.07-8986"}], "href": "https://doi.org/10.1096/fj.07-8986"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17898086"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17898086"}]}]}]}