{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n ATP5PD, which encodes a subunit of the mitochondrial ATP synthase complex (often referred to as ATP5H or the d subunit), plays a critical role in oxidative phosphorylation by contributing to the assembly, stability, and function of the enzyme complex responsible for cellular ATP production. Alterations in ATP5PD expression influence mitochondrial bioenergetics under various stress conditions. For example, genetic variation at the ATP5H/KCTD2 locus has been implicated in Alzheimer’s disease, where proper ATP synthase function is essential not only for adequate ATP generation but also for maintaining neuronal membrane potential and counteracting hyperpolarization during cellular stress."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " Similarly, reduced ATP5PD protein levels observed in models of spinocerebellar ataxia type‐1 correlate with decreased ATP synthesis and broader disruptions in mitochondrial energy metabolism, suggesting that even modest dysregulation of this subunit can lead to impaired neuronal function."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": " In addition, transcriptomic analyses in late‐onset Alzheimer’s disease have identified differential expression of ATP5PD alongside other mitochondrial genes, reinforcing its role as part of the broader mitochondrial dysfunction that characterizes neurodegenerative pathology."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": " Furthermore, alterations in ATP5PD expression in gastrointestinal tissues—such as elevated levels observed in the colonic mucosa of patients with irritable bowel syndrome with diarrhea—appear to be associated with abnormal ATP levels and disrupted energy metabolism, highlighting its importance not only in the central nervous system but also in peripheral tissues."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Together, these findings underscore that ATP5PD is integral to the maintenance of mitochondrial function and cellular energy homeostasis. Its dysregulation is linked to a spectrum of disorders—ranging from neurodegenerative diseases to gastrointestinal dysfunction—by modulating ATP production and cellular responses to metabolic stress.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "M Boada, C Antúnez, R Ramírez-Lorca, et al. "}, {"type": "b", "children": [{"type": "t", "text": "ATP5H/KCTD2 locus is associated with Alzheimer's disease risk."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Psychiatry (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/mp.2013.86"}], "href": "https://doi.org/10.1038/mp.2013.86"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23857120"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23857120"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Ivelisse Sánchez, Eudald Balagué, Antoni Matilla-Dueñas "}, {"type": "b", "children": [{"type": "t", "text": "Ataxin-1 regulates the cerebellar bioenergetics proteome through the GSK3β-mTOR pathway which is altered in Spinocerebellar ataxia type 1 (SCA1)."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Mol Genet (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/hmg/ddw242"}], "href": "https://doi.org/10.1093/hmg/ddw242"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27466200"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27466200"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Shubhabrata Mukherjee, Joshua C Russell, Daniel T Carr, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Systems biology approach to late-onset Alzheimer's disease genome-wide association study identifies novel candidate genes validated using brain expression data and Caenorhabditis elegans experiments."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Alzheimers Dement (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.jalz.2017.01.016"}], "href": "https://doi.org/10.1016/j.jalz.2017.01.016"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28242297"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28242297"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Jürgen Borlak, Prashant Singh, Giuseppe Gazzana "}, {"type": "b", "children": [{"type": "t", "text": "Proteome mapping of epidermal growth factor induced hepatocellular carcinomas identifies novel cell metabolism targets and mitogen activated protein kinase signalling events."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "BMC Genomics (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1186/s12864-015-1312-z"}], "href": "https://doi.org/10.1186/s12864-015-1312-z"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25872475"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25872475"}]}]}]}