{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nNME3 functions as a multifunctional nucleoside diphosphate kinase that localizes to the mitochondrial outer membrane, where it plays a critical role in maintaining mitochondrial dynamics and energy metabolism. It facilitates mitochondrial fusion through both its catalytic activity and its ability to tether mitochondria – for example, by binding phosphatidic acid generated by PLD6 and interacting with fusion mediators such as MFN1/2 – thereby ensuring proper metabolic adaptation under stress conditions and contributing to efficient DNA repair by providing site‐specific dNTP synthesis via interactions with Tip60 and RNR. Moreover, depletion of NME3 disrupts mitochondrial morphology and increases oxidative stress that leads to genome instability, with further implications for organelle division and lipid metabolism."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "5"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn addition to its mitochondrial functions, NME3 influences tumor biology by modulating cell motility, proliferation, and proinflammatory signaling. Its expression—referred to in some studies as NM23-H3 or DR-nm23—has been associated with reduced migratory capacity of cancer cells in laryngeal and colorectal carcinomas. Furthermore, NME3 acts as a positive regulator downstream of toll-like receptor 5, where it enhances NFκB-mediated inflammatory responses that may potentiate anti-tumor immunity."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "6", "end_ref": "8"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond these roles, NME3 is integral to broader aspects of cellular organization. It localizes to basal bodies in ciliated cells, where its interactions with nephronophthisis proteins underscore a role in ciliary function and developmental homeostasis. High-resolution structural studies of its NDP kinase domain further elucidate its nucleotide binding and phosphotransferase activity, shedding light on the mechanistic basis for its diverse roles in cell signaling, organellar dynamics, and genome maintenance."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Chih-Wei Chen, Hong-Ling Wang, Ching-Wen Huang, et al. 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