{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nTBC1D15, a member of the TBC domain family, functions primarily as a Rab7-specific GTPase-activating protein that modulates late endosomal trafficking and lysosomal morphology. By stimulating the intrinsic GTPase activity of Rab7, TBC1D15 promotes lysosomal fragmentation and impacts the fusion events required for proper endosome–lysosome interactions."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn addition to its role in vesicular trafficking, TBC1D15 is a key regulator of mitochondrial dynamics. Under conditions of cellular stress such as acute myocardial infarction, TBC1D15 modulates the contacts between mitochondria and lysosomes to ensure effective clearance of damaged mitochondria via mitophagy. Moreover, in the context of innate immune responses, TBC1D15-mediated control of mitochondrial fission counteracts the suppression of the STING DNA-sensing pathway, thereby influencing downstream antiviral signaling."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nTBC1D15 further contributes to cell fate decisions by perturbing the Numb–p53 complex. Its amino-terminal domain dislodges p53 from Numb, leading to p53 degradation and thereby enhancing stem cell self-renewal and pluripotency—a function that supports oncogenic processes. Notably, cellular levels of TBC1D15 are finely tuned by nutrient status through autophagy‐mediated degradation, underscoring its role as a metabolic sensor linking cell survival, differentiation, and tumor expansion."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn contrast, a separate study focused on Spata17—although not directly linked to TBC1D15—reveals that the Spata17 protein is predominantly expressed in spermatids and can trigger apoptosis in male germ cell lines, suggesting its involvement in spermatogenesis and the regulation of germ cell fate."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Xiang-Ming Zhang, Bong Walsh, Christina A Mitchell, et al. "}, {"type": "b", "children": [{"type": "t", "text": "TBC domain family, member 15 is a novel mammalian Rab GTPase-activating protein with substrate preference for Rab7."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem Biophys Res Commun (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbrc.2005.07.070"}], "href": "https://doi.org/10.1016/j.bbrc.2005.07.070"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16055087"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16055087"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Eigen R Peralta, Brent C Martin, Aimee L Edinger "}, {"type": "b", "children": [{"type": "t", "text": "Differential effects of TBC1D15 and mammalian Vps39 on Rab7 activation state, lysosomal morphology, and growth factor dependence."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M110.111633"}], "href": "https://doi.org/10.1074/jbc.M110.111633"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20363736"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20363736"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Dohyeong Kwon, Eunbyeol Park, Suk-Jo Kang "}, {"type": "b", "children": [{"type": "t", "text": "Stimulator of IFN genes-mediated DNA-sensing pathway is suppressed by NLRP3 agonists and regulated by mitofusin 1 and TBC1D15, mitochondrial dynamics mediators."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "FASEB J (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1096/fj.201700328R"}], "href": "https://doi.org/10.1096/fj.201700328R"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28729291"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28729291"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Wenjun Yu, Shiqun Sun, Haixia Xu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "TBC1D15/RAB7-regulated mitochondria-lysosome interaction confers cardioprotection against acute myocardial infarction-induced cardiac injury."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Theranostics (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.7150/thno.46883"}], "href": "https://doi.org/10.7150/thno.46883"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33042281"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33042281"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Douglas E Feldman, Chialin Chen, Vasu Punj, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The TBC1D15 oncoprotein controls stem cell self-renewal through destabilization of the Numb-p53 complex."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0057312"}], "href": "https://doi.org/10.1371/journal.pone.0057312"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23468968"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23468968"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Yun Deng, Liang-Sha Hu, Guang-Xiu Lu "}, {"type": "b", "children": [{"type": "t", "text": "Expression and identification of a novel apoptosis gene Spata17 (MSRG-11) in mouse spermatogenic cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Acta Biochim Biophys Sin (Shanghai) (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/j.1745-7270.2006.00125.x"}], "href": "https://doi.org/10.1111/j.1745-7270.2006.00125.x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16395525"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16395525"}]}]}]}