{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nMTIF3 is a nucleus‐encoded mitochondrial translation initiation factor that plays a pivotal role in the formation of the initiation complex on the mitochondrial ribosome. This function is critical for the translation of mitochondrial mRNAs that encode essential components of the oxidative phosphorylation system, notably influencing ATP synthase assembly as shown in human cell models. Disruption of MTIF3 expression by CRISPR‐Cas9 editing in cultured cells leads to selective decreases in the translation of key mRNAs (e.g., ATP6), reduced mitochondrial respiration, and impaired fatty acid oxidation in adipocytes, demonstrating its central role in mitochondrial protein synthesis and energy homeostasis."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "3"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its canonical function in mitochondrial translation, genetic variation in the MTIF3 gene has been implicated in the pathogenesis of neurodegenerative disorders such as Parkinson’s disease. Several independent case–control studies have reported that specific MTIF3 polymorphisms are associated with altered gene expression and compromised mitochondrial function, which may lead to increased oxidative stress and neuronal vulnerability. These findings suggest that even subtle changes in MTIF3 function can influence the biosynthetic capacity of mitochondria and thus contribute to the development of Parkinson’s disease."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "4", "end_ref": "6"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nMTIF3’s influence has also been explored in metabolic regulation and weight control. In lifestyle intervention studies directed at reducing obesity, a common variant in MTIF3 (rs1885988) was associated with greater weight loss, suggesting that genetic modulation of mitochondrial translation may affect adipocyte bioenergetics and energy expenditure. Conversely, while investigations evaluating nuclear‐encoded mitochondrial proteins in type II diabetes and weight loss after bariatric surgery have generated mixed results, they underscore the complexity of MTIF3’s contributions to systemic metabolism and body weight regulation."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "7", "end_ref": "9"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "I V Chicherin, M V Baleva, S A Levitskii, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Mitochondrial Translation Initiation Factor 3: Structure, Functions, Interactions, and Implication in Human Health and Disease."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochemistry (Mosc) (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1134/S0006297919100031"}], "href": "https://doi.org/10.1134/S0006297919100031"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31694510"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31694510"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Ivan V Chicherin, Maria V Baleva, Sergey A Levitskii, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Initiation Factor 3 is Dispensable For Mitochondrial Translation in Cultured Human Cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Sci Rep (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41598-020-64139-5"}], "href": "https://doi.org/10.1038/s41598-020-64139-5"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32346061"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32346061"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Mi Huang, Daniel Coral, Hamidreza Ardalani, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Identification of a weight loss-associated causal eQTL in "}, {"type": "a", "children": [{"type": "t", "text": "i"}], "href": "i"}, {"type": "t", "text": "MTIF3"}, {"type": "a", "children": [{"type": "t", "text": "/i"}], "href": "/i"}, {"type": "t", "text": " and the effects of "}, {"type": "a", "children": [{"type": "t", "text": "i"}], "href": "i"}, {"type": "t", "text": "MTIF3"}, {"type": "a", "children": [{"type": "t", "text": "/i"}], "href": "/i"}, {"type": "t", "text": " deficiency on human adipocyte function."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Elife (2023)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.7554/eLife.84168"}], "href": "https://doi.org/10.7554/eLife.84168"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "36876906"}], "href": "https://pubmed.ncbi.nlm.nih.gov/36876906"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Nadine Abahuni, Suzana Gispert, Peter Bauer, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Mitochondrial translation initiation factor 3 gene polymorphism associated with Parkinson's disease."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Neurosci Lett (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.neulet.2006.12.053"}], "href": "https://doi.org/10.1016/j.neulet.2006.12.053"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17267121"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17267121"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Bahareh Behrouz, Carles Vilariño-Güell, Michael G Heckman, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Mitochondrial translation initiation factor 3 polymorphism and Parkinson's disease."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Neurosci Lett (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.neulet.2010.09.059"}], "href": "https://doi.org/10.1016/j.neulet.2010.09.059"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20887776"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20887776"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Anna Anvret, Caroline Ran, Marie Westerlund, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Possible involvement of a mitochondrial translation initiation factor 3 variant causing decreased mRNA levels in Parkinson's disease."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Parkinsons Dis (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.4061/2010/491751"}], "href": "https://doi.org/10.4061/2010/491751"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20976088"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20976088"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Erwin Reiling, Jana V van Vliet-Ostaptchouk, Esther van 't Riet, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Genetic association analysis of 13 nuclear-encoded mitochondrial candidate genes with type II diabetes mellitus: the DAMAGE study."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Eur J Hum Genet (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ejhg.2009.4"}], "href": "https://doi.org/10.1038/ejhg.2009.4"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19209188"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19209188"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "George D Papandonatos, Qing Pan, Nicholas M Pajewski, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Genetic Predisposition to Weight Loss and Regain With Lifestyle Intervention: Analyses From the Diabetes Prevention Program and the Look AHEAD Randomized Controlled Trials."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Diabetes (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.2337/db15-0441"}], "href": "https://doi.org/10.2337/db15-0441"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26253612"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26253612"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Laura J Rasmussen-Torvik, Abigail S Baldridge, Jennifer A Pacheco, et al. "}, {"type": "b", "children": [{"type": "t", "text": "rs4771122 Predicts Multiple Measures of Long-Term Weight Loss After Bariatric Surgery."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Obes Surg (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s11695-015-1872-7"}], "href": "https://doi.org/10.1007/s11695-015-1872-7"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26337695"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26337695"}]}]}]}