{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nPDHA1, the E1α catalytic subunit of the pyruvate dehydrogenase complex, serves as a critical metabolic “gatekeeper” by converting pyruvate into acetyl‐CoA—a reaction that bridges glycolysis with the tricarboxylic acid cycle. Its activity is subject to dynamic control by reversible phosphorylation (both serine‐ and tyrosine‐directed modifications), which regulates substrate access and flux through mitochondrial oxidation. In addition, external signals such as extracellular matrix attachment, growth factors, and insulin further modulate PDHA1 function, thereby adapting energetic output to cellular demands."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "6"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nAltered PDHA1 function—through genetic mutations or dysregulated expression—has been implicated in a broad spectrum of diseases. Inherited PDHA1 mutations underlie pyruvate dehydrogenase complex deficiencies, manifesting as neonatal lactic acidosis, diverse neurodevelopmental abnormalities, characteristic neuroimaging patterns, and episodic metabolic decompensation. Somatic defects in PDHA1 are also increasingly recognized in various human cancers including prostate, gastric, colorectal, hepatocellular, and head and neck carcinomas, where reduced PDHA1 activity shifts metabolism toward aerobic glycolysis (the Warburg effect), promotes lipid biosynthesis and tumor growth, and is associated with poor clinical outcomes. Structural analyses of PDHA1 mutants have further illuminated the molecular basis for enzymatic inactivation observed in these pathological settings."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "7", "end_ref": "24"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its roles in energy metabolism and oncogenesis, emerging studies indicate that PDHA1 participates in broader regulatory networks influencing immune responses and cellular homeostasis. Autoimmune reactivity to PDHA1 epitopes has been documented in certain patients, implicating it in immune‐mediated disease processes, while its post‐translational modification and subcellular redistribution (including nuclear translocation) have been associated with alterations in histone acetylation, tumor cell stemness, and resistance to cytotoxic insults. Moreover, experimental models demonstrate that deliberate modulation of PDHA1 function—whether by genetic ablation or pharmacological interventions—can reprogram tumor metabolism and attenuate inflammatory or ischemic injury in conditions such as sepsis‐induced kidney injury and diabetic nephropathy."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "25", "end_ref": "32"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Yasuaki Hiromasa, Tetsuro Fujisawa, Yoichi Aso, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "Acute flaccid paralysis as initial symptom in 4 patients with novel E1alpha mutations of the pyruvate dehydrogenase complex."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Neuropediatrics (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1055/s-2006-924555"}], "href": "https://doi.org/10.1055/s-2006-924555"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16967364"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16967364"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Maria João Silva, Ana Pinheiro, Filomena Eusébio, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "Mutational study in the PDHA1 gene of 40 patients suspected of pyruvate dehydrogenase complex deficiency."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Clin Genet (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/j.1399-0004.2009.01313.x"}], "href": "https://doi.org/10.1111/j.1399-0004.2009.01313.x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20002461"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20002461"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "Nicholas Ah Mew, Johanna B Loewenstein, Nadja Kadom, et al. "}, {"type": "b", "children": [{"type": "t", "text": "MRI features of 4 female patients with pyruvate dehydrogenase E1 alpha deficiency."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Pediatr Neurol (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.pediatrneurol.2011.02.003"}], "href": "https://doi.org/10.1016/j.pediatrneurol.2011.02.003"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21723463"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21723463"}]}, {"type": "r", "ref": 13, "children": [{"type": "t", "text": "Ruchi Sharma, Mark J Sharrard, Daniel J Connolly, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "Combined evaluation of hexokinase 2 and phosphorylated pyruvate dehydrogenase-E1α in invasive front lesions of colorectal tumors predicts cancer metabolism and patient prognosis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Sci (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/cas.12487"}], "href": "https://doi.org/10.1111/cas.12487"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25060325"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25060325"}]}, {"type": "r", "ref": 18, "children": [{"type": "t", "text": "Fabao Liu, Weiying Zhang, Xiaona You, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The oncoprotein HBXIP promotes glucose metabolism reprogramming via downregulating SCO2 and PDHA1 in breast cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oncotarget (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.18632/oncotarget.4508"}], "href": "https://doi.org/10.18632/oncotarget.4508"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26309161"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26309161"}]}, {"type": "r", "ref": 19, "children": [{"type": "t", "text": "Jingjing Chen, Ilaria Guccini, Diletta Di Mitri, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Compartmentalized activities of the pyruvate dehydrogenase complex sustain lipogenesis in prostate cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Genet (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41588-017-0026-3"}], "href": "https://doi.org/10.1038/s41588-017-0026-3"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29335542"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29335542"}]}, {"type": "r", "ref": 20, "children": [{"type": "t", "text": "Jihong Sun, Jingjing Li, Zhixian Guo, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "PGC1α promotes cholangiocarcinoma metastasis by upregulating PDHA1 and MPC1 expression to reverse the Warburg effect."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Death Dis (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41419-018-0494-0"}], "href": "https://doi.org/10.1038/s41419-018-0494-0"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29700317"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29700317"}]}, {"type": "r", "ref": 22, "children": [{"type": "t", "text": "Matthew J Whitley, Palaniappa Arjunan, Natalia S Nemeria, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "Determination of Pyruvate Metabolic Fates Modulates Head and Neck Tumorigenesis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Neoplasia (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.neo.2019.04.007"}], "href": "https://doi.org/10.1016/j.neo.2019.04.007"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31100640"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31100640"}]}, {"type": "r", "ref": 24, "children": [{"type": "t", "text": "Kuntal Sen, George Grahame, Jirair K Bedoyan, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Novel presentations associated with a PDHA1 variant - Alternating hemiplegia in Hemizygote proband and Guillain Barre Syndrome in Heterozygote mother."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Eur J Paediatr Neurol (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.ejpn.2021.01.006"}], "href": "https://doi.org/10.1016/j.ejpn.2021.01.006"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33592356"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33592356"}]}, {"type": "r", "ref": 25, "children": [{"type": "t", "text": "Tsutomu Mori, Kazuo Ono, Masatoshi Hakozaki, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Epitope mapping on E1alpha subunit of pyruvate dehydrogenase complex with autoantibodies of patients with primary biliary cirrhosis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Liver Int (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1034/j.1478-3231.2003.00857.x"}], "href": "https://doi.org/10.1034/j.1478-3231.2003.00857.x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "14708897"}], "href": "https://pubmed.ncbi.nlm.nih.gov/14708897"}]}, {"type": "r", "ref": 26, "children": [{"type": "t", "text": "M Magner, K Vinšová, M Tesařová, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Two patients with clinically distinct manifestation of pyruvate dehydrogenase deficiency due to mutations in PDHA1 gene."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Prague Med Rep (2011)"}]}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21470495"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21470495"}]}, {"type": "r", "ref": 27, "children": [{"type": "t", "text": "Israa Sharkia, Tal Hadad Erlich, Nadine Landolina, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Pyruvate dehydrogenase has a major role in mast cell function, and its activity is regulated by mitochondrial microphthalmia transcription factor."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Allergy Clin Immunol (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.jaci.2016.09.047"}], "href": "https://doi.org/10.1016/j.jaci.2016.09.047"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27871875"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27871875"}]}, {"type": "r", "ref": 28, "children": [{"type": "t", "text": "Yali Zhong, Xiaoli Li, Yasai Ji, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Pyruvate dehydrogenase expression is negatively associated with cell stemness and worse clinical outcome in prostate cancers."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oncotarget (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.18632/oncotarget.14527"}], "href": "https://doi.org/10.18632/oncotarget.14527"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28076853"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28076853"}]}, {"type": "r", "ref": 29, "children": [{"type": "t", "text": "Wei-Ye Shi, Xiao Yang, Bo Huang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "NOK mediates glycolysis and nuclear PDC associated histone acetylation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Front Biosci (Landmark Ed) (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.2741/4572"}], "href": "https://doi.org/10.2741/4572"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28410146"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28410146"}]}, {"type": "r", "ref": 30, "children": [{"type": "t", "text": "Yajuan Zhang, Ming Zhao, Hong Gao, et al. "}, {"type": "b", "children": [{"type": "t", "text": "MAPK signalling-induced phosphorylation and subcellular translocation of PDHE1α promotes tumour immune evasion."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Metab (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s42255-022-00543-7"}], "href": "https://doi.org/10.1038/s42255-022-00543-7"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "35315437"}], "href": "https://pubmed.ncbi.nlm.nih.gov/35315437"}]}, {"type": "r", "ref": 31, "children": [{"type": "t", "text": "Chung-Hsing Wang, Wen-Li Lu, Shang-Lun Chiang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "T Cells Mediate Kidney Tubular Injury via Impaired PDHA1 and Autophagy in Type 1 Diabetes."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Clin Endocrinol Metab (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1210/clinem/dgac378"}], "href": "https://doi.org/10.1210/clinem/dgac378"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "35731579"}], "href": "https://pubmed.ncbi.nlm.nih.gov/35731579"}]}, {"type": "r", "ref": 32, "children": [{"type": "t", "text": "Sheng An, Yi Yao, Hongbin Hu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "PDHA1 hyperacetylation-mediated lactate overproduction promotes sepsis-induced acute kidney injury via Fis1 lactylation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Death Dis (2023)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41419-023-05952-4"}], "href": "https://doi.org/10.1038/s41419-023-05952-4"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "37479690"}], "href": "https://pubmed.ncbi.nlm.nih.gov/37479690"}]}]}]}