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Hepatocyte mitochondrial aquaporin\u20108 (AQP8) channels have been involved in ammonia\u2010derived ureagenesis. Herein, we studied whether the adenoviral gene transfer of human AQP8 (hAQP8) to hepatocyte mitochondria enhances ammonia conversion to urea. Using primary cultured rat hepatocytes, we first confirmed the mitochondrial expression of hAQP8 and then, using unlabeled or <jats:sup>15<\/jats:sup>N\u2010labeled ammonia, we demonstrated that the urea synthesis was significantly enhanced in hAQP8\u2010transduced hepatocytes. Studies using isolated hAQP8\u2010expressing mitochondria also showed an increased ammonia metabolism. hAQP8 transduction was able to recover the impaired ammonia\u2010derived ureagenesis in hepatotoxin\u2010treated hepatocytes. Our data suggest that mitochondrially\u2010expressed hAQP8 enhances and improves hepatocyte ammonia conversion to urea, a finding with potential therapeutic implications for liver disease with impaired ammonia detoxification.<\/jats:p>","DOI":"10.1002\/bit.27901","type":"journal-article","created":{"date-parts":[[2021,7,22]],"date-time":"2021-07-22T08:57:15Z","timestamp":1626944235000},"page":"4331-4337","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Enhanced ammonia detoxification to urea in hepatocytes transduced with human aquaporin\u20108 gene"],"prefix":"10.1002","volume":"118","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7387-8653","authenticated-orcid":false,"given":"Alejo M.","family":"Capiglioni","sequence":"first","affiliation":[{"name":"Instituto de Fisiolog\u00eda Experimental, Consejo Nacional de Investigaciones Cient\u00edficas y T\u00e9cnicas, Facultad de Ciencias Bioqu\u00edmicas y Farmac\u00e9uticas Universidad Nacional de Rosario Rosario Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriela L.","family":"M\u00fcller","sequence":"additional","affiliation":[{"name":"Centro de Estudios Fotosint\u00e9ticos y Bioqu\u00edmicos (CEFOBI\u2010CONICET), Facultad de Ciencias Bioqu\u00edmicas y Farmac\u00e9uticas Universidad Nacional de Rosario Rosario Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julieta","family":"Marrone","sequence":"additional","affiliation":[{"name":"Instituto de Fisiolog\u00eda Experimental, Consejo Nacional de Investigaciones Cient\u00edficas y T\u00e9cnicas, Facultad de Ciencias Bioqu\u00edmicas y Farmac\u00e9uticas Universidad Nacional de Rosario Rosario Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria L.","family":"Alvarez","sequence":"additional","affiliation":[{"name":"Instituto de Fisiolog\u00eda Experimental, Consejo Nacional de Investigaciones Cient\u00edficas y T\u00e9cnicas, Facultad de Ciencias Bioqu\u00edmicas y Farmac\u00e9uticas Universidad Nacional de Rosario Rosario Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ra\u00fal A.","family":"Marinelli","sequence":"additional","affiliation":[{"name":"Instituto de Fisiolog\u00eda Experimental, Consejo Nacional de Investigaciones Cient\u00edficas y T\u00e9cnicas, Facultad de Ciencias Bioqu\u00edmicas y Farmac\u00e9uticas Universidad Nacional de Rosario Rosario Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,7,28]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1201\/b19017-12"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.C400595200"},{"issue":"105632","key":"e_1_2_8_4_1","first-page":"1","article-title":"Data of ureagenesis from ammonia, glutamine and alanine, and mitochondrial aquaporin\u20108 expression in thioacetamide\u2010treated hepatocytes","volume":"30","author":"Capiglioni A. 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