{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n The haloacid dehalogenase‐like hydrolase domain‐containing protein 3 (HDHD3) has been implicated in two distinct biological contexts based on findings from multiple studies. In the setting of colorectal lesion development, HDHD3 is one of several genes that become frequently hypermethylated during the progression from aberrant crypt foci to sessile serrated adenomas/polyps and ultimately to cancer, leading to its transcriptional silencing and suggesting that loss of its function may be associated with neoplastic progression."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n In contrast, HDHD3 has also been identified as a component of mitochondrial protein clusters involved in energy maintenance and homeostasis. In liver tissue, for example, its expression is part of a group of proteins regulated by sericin treatment that preserves mitochondrial architecture under hypercholesterolaemic conditions, and its upregulation is observed under high polyunsaturated fatty acid dietary regimens, suggesting a role in metabolic adaptations."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": " Similarly, in a diabetic kidney disease model presenting with alpha‑2u globulin nephropathy, HDHD3 expression is significantly increased alongside other mitochondrial markers, correlating with altered mitochondrial function and structural adaptation in renal tissue."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Together, these findings highlight a dual aspect of HDHD3 function: on one hand, its epigenetic silencing in the colorectal neoplasia sequence may reflect a pathogenic mechanism in tumor progression, while on the other, its regulated expression in liver and kidney underscores a role in maintaining mitochondrial integrity and cellular energy balance under conditions of metabolic stress.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "A Inoue, K Okamoto, Y Fujino, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "Adaptive effect of sericin on hepatic mitochondrial conformation through its regulation of apoptosis, autophagy and energy maintenance: a proteomics approach."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Sci Rep (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41598-018-33372-4"}], "href": "https://doi.org/10.1038/s41598-018-33372-4"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30297713"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30297713"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Kamila P Liput, Adam Lepczyński, Agata Nawrocka, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Effects of Three-Month Administration of High-Saturated Fat Diet and High-Polyunsaturated Fat Diets with Different Linoleic Acid (LA, C18:2n-6) to α-Linolenic Acid (ALA, C18:3n-3) Ratio on the Mouse Liver Proteome."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nutrients (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3390/nu13051678"}], "href": "https://doi.org/10.3390/nu13051678"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34063343"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34063343"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Kanchana Kengkoom, Wannee Angkhasirisap, Tapanee Kanjanapruthipong, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Streptozotocin induces alpha-2u globulin nephropathy in male rats during diabetic kidney disease."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "BMC Vet Res (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1186/s12917-021-02814-z"}], "href": "https://doi.org/10.1186/s12917-021-02814-z"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33663503"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33663503"}]}]}]}