{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nRecent investigations into mitochondrial energy metabolism and neuroactive compound synthesis have underscored the importance of enzymes with dual functionalities in the brain. For example, studies have shown that blast-induced traumatic brain injury is associated with a transient decline in neuronal ATP production that correlates with a reduction in the activity of enzymes such as glutamate oxaloacetate transaminase 2 (GOT2). In parallel, research on the kynurenine pathway has illuminated how mitochondrial aspartate aminotransferase (mAspAT)—which also functions as a kynurenine aminotransferase (KAT)—contributes to the biosynthesis of neuroactive kynurenic acid. These findings highlight key metabolic nodes in neurological function and energy homeostasis."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "3"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nComplementary studies have extended these insights into disease models where mitochondrial dysfunction and enzyme regulation play pivotal roles. For instance, upregulation of GOT2 has been implicated in preserving ATP production in neurodegenerative conditions such as secondary progressive multiple sclerosis, while alterations in aspartate aminotransferase activity in macrophages emphasize its impact on inflammatory signaling. Additional work focusing on skeletal muscle metabolism in IL-6–deficient models and in C2C12 myocytes with GOT2 knockdown reinforces the idea that disturbances in mitochondrial transaminase activity can have widespread metabolic and inflammatory consequences."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "4", "end_ref": "7"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nEmerging evidence also implicates small nucleolar RNAs (snoRNAs) in the modulation of these metabolic pathways. In particular, research into hepatocellular carcinoma has suggested that polymorphisms within snoRNAs may affect both their expression and the function of their host genes, with potential downstream effects on cellular metabolism. Although the direct role of SNORD105 has yet to be fully elucidated, by analogy with other snoRNAs its canonical function is likely to involve the posttranscriptional modification of ribosomal RNA. This activity may indirectly influence the translation and stability of key metabolic enzymes—such as GOT2—and thus participate in the fine-tuning of mitochondrial energy production and other critical cellular processes."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": ""}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Qian Han, Tao Cai, Danilo A Tagle, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "Biochemical and structural characterization of mouse mitochondrial aspartate aminotransferase, a newly identified kynurenine aminotransferase-IV."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biosci Rep (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1042/BSR20100117"}], "href": "https://doi.org/10.1042/BSR20100117"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20977429"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20977429"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Peethambaran Arun, Rania Abu-Taleb, Samuel Oguntayo, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Acute mitochondrial dysfunction after blast exposure: potential role of mitochondrial glutamate oxaloacetate transaminase."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Neurotrauma (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1089/neu.2012.2834"}], "href": "https://doi.org/10.1089/neu.2012.2834"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23600763"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23600763"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "A Chabowski, M Zmijewska, J Gorski, et al. "}, {"type": "b", "children": [{"type": "t", "text": "IL-6 deficiency increases fatty acid transporters and intramuscular lipid content in red but not white skeletal muscle."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Physiol Pharmacol (2008)"}]}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19258660"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19258660"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Josephe A Honorat, Yuji Nakatsuji, Mikito Shimizu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Febuxostat ameliorates secondary progressive experimental autoimmune encephalomyelitis by restoring mitochondrial energy production in a GOT2-dependent manner."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0187215"}], "href": "https://doi.org/10.1371/journal.pone.0187215"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29107957"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29107957"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Zhigang Zhu, Lulu Zhang, Qinghua Chen, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Macrophage-derived sulfur dioxide is a novel inflammation regulator."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem Biophys Res Commun (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbrc.2020.02.013"}], "href": "https://doi.org/10.1016/j.bbrc.2020.02.013"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32057367"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32057367"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Ritu Som, Brian D Fink, Liping Yu, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "An SNP reducing SNORD105 and PPAN expression decreases the risk of hepatocellular carcinoma in a Chinese population."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Clin Lab Anal (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/jcla.24095"}], "href": "https://doi.org/10.1002/jcla.24095"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34741342"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34741342"}]}]}]}