{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nThe pyruvate dehydrogenase complex plays a central role in cellular energy metabolism by converting pyruvate into acetyl‐CoA, and its catalytic E1α subunit is encoded by two distinct genes. In somatic tissues, PDHA1 is ubiquitously expressed and has been implicated in metabolic reprogramming in cancer cells."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " In contrast, PDHA2 is expressed exclusively in spermatogenic cells, where a developmental switch—occurring in spermatocytes—ensures continuous mitochondrial function and an uninterrupted supply of energy critical for germ cell viability."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": "\n \n \nThe tightly controlled, tissue-specific expression of PDHA2 is largely governed by epigenetic mechanisms. Studies have demonstrated that the methylation status of specific CpG islands within the PDHA2 gene is key to its regulation; while hypermethylation represses its expression in somatic tissues"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": ", full demethylation of a CpG island within the coding region is crucial for gene activation in the testis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": "\n \n \nClinically, PDHA2 holds significance as a candidate gene for male infertility. Variants within PDHA2 that affect its function have been linked to abnormalities in sperm motility and energy metabolism, underscoring its fundamental role in spermatogenesis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": " Collectively, these findings illuminate a model in which PDHA2 expression is optimized in germ cells through precise epigenetic modulation, thereby guaranteeing robust energy production required for proper sperm function while contrasting with the somatic functions of its homolog PDHA1."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Zhuo Liu, Miao Yu, Bingyuan Fei, et al. "}, {"type": "b", "children": [{"type": "t", "text": "miR‑21‑5p targets PDHA1 to regulate glycolysis and cancer progression in gastric cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oncol Rep (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3892/or.2018.6695"}], "href": "https://doi.org/10.3892/or.2018.6695"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30226598"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30226598"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Ana Pinheiro, Maria João Silva, Inês Graça, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "Demethylation of the coding region triggers the activation of the human testis-specific PDHA2 gene in somatic tissues."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0038076"}], "href": "https://doi.org/10.1371/journal.pone.0038076"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22675509"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22675509"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Yeşerin Yıldırım, Toufik Ouriachi, Ute Woehlbier, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Linked homozygous BMPR1B and PDHA2 variants in a consanguineous family with complex digit malformation and male infertility."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Eur J Hum Genet (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41431-018-0121-7"}], "href": "https://doi.org/10.1038/s41431-018-0121-7"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29581481"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29581481"}]}]}]}