{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T10:47:57Z","timestamp":1792406877818,"version":"4.4.0"},"reference-count":24,"publisher":"Bioscientifica","issue":"1","license":[{"start":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T00:00:00Z","timestamp":1791417600000},"content-version":"vor","delay-in-days":7,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["journals.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2026,10,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Graphical abstract<\/jats:title>\n                    <jats:p\/>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Abstract<\/jats:title>\n                    <jats:p>Obesity and diabetes arise from disrupted energy homeostasis, underscoring the need to identify mechanisms that enhance energy expenditure. Brown adipose tissue dissipates energy through mitochondria-dependent non-shivering thermogenesis; however, the transcriptional regulators coordinating this process remain incompletely defined. Here, we investigated the role of activating transcription factor 5 in thermogenic programming and mitochondrial metabolism in brown adipocytes using in vivo and in vitro models. Cold exposure and \u03b23-adrenergic stimulation induced activating transcription factor 5 expression in brown adipose tissue and differentiated adipocytes, accompanied by activation of thermogenic gene programs. Mechanistically, activating transcription factor 5 functioned downstream of a nuclear protein kinase A\u2013extracellular signal-regulated kinase pathway, whose nuclear activation was required for its induction and for upregulation of uncoupling protein 1. Loss of activating transcription factor 5 impaired thermogenic gene expression, reduced mitochondrial stress response and lipolytic programs, diminished mitochondrial oxidative capacity, and suppressed fatty acid oxidation, including reduced incorporation of fatty acid\u2013derived carbons into the tricarboxylic acid cycle. Transcriptomic analysis revealed coordinated repression of pathways related to fatty acid oxidation, oxidative phosphorylation, and thermogenesis in activating transcription factor 5\u2013deficient adipocytes. Live-cell imaging further confirmed that \u03b23-adrenergic stimulation selectively enhanced nuclear kinase activity, establishing a nuclear-localized signaling axis. Together, these findings identify activating transcription factor 5 as a key transcriptional regulator linking mitochondrial metabolism and thermogenic gene expression, supporting its potential as a therapeutic target for enhancing energy expenditure in metabolic disease.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1530\/joe-26-0101","type":"journal-article","created":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T09:11:07Z","timestamp":1791450667000},"update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-5","source":"Crossref","is-referenced-by-count":0,"title":["A nuclear ERK\u2013ATF5 axis coordinates mitochondrial metabolism and thermogenic gene expression in brown adipocytes"],"prefix":"10.1530","volume":"271","author":[{"given":"Hyo Ju","family":"Jang","sequence":"first","affiliation":[{"name":"Laboratory of Endocrinology and Immune System, Chungnam National University School of Medicine 1 , ,","place":["Daejeon, Republic of Korea"]},{"name":"Department of Medical Science, Chungnam National University School of Medicine 2 , ,","place":["Daejeon, Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yeongjun","family":"Suh","sequence":"additional","affiliation":[{"name":"Department of Life Sciences, Gwangju Institute of Science and Technology 3 , ,","place":["Gwangju, Republic of Korea"]},{"name":"Integrated Institute of Biomedical Research, Gwangju Institute of Science and Technology 4 , ,","place":["Gwangju, Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingwen","family":"Tian","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery, The Sixth Affiliated Hospital of Sun Yat-sen University 5 , , ,","place":["Guangzhou, Guangdong, P.R. China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ho Yeop","family":"Lee","sequence":"additional","affiliation":[{"name":"Laboratory of Endocrinology and Immune System, Chungnam National University School of Medicine 1 , ,","place":["Daejeon, Republic of Korea"]},{"name":"Department of Medical Science, Chungnam National University School of Medicine 2 , ,","place":["Daejeon, Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ji Sun","family":"Moon","sequence":"additional","affiliation":[{"name":"Laboratory of Endocrinology and Immune System, Chungnam National University School of Medicine 1 , ,","place":["Daejeon, Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ha Thi","family":"Nga","sequence":"additional","affiliation":[{"name":"Laboratory of Endocrinology and Immune System, Chungnam National University School of Medicine 1 , ,","place":["Daejeon, Republic of Korea"]},{"name":"Department of Medical Science, Chungnam National University School of Medicine 2 , ,","place":["Daejeon, Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thi Linh","family":"Nguyen","sequence":"additional","affiliation":[{"name":"Laboratory of Endocrinology and Immune System, Chungnam National University School of Medicine 1 , ,","place":["Daejeon, Republic of Korea"]},{"name":"Department of Medical Science, Chungnam National University School of Medicine 2 , ,","place":["Daejeon, Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alfin Mohammad","family":"Abdillah","sequence":"additional","affiliation":[{"name":"Laboratory of Endocrinology and Immune System, Chungnam National University School of Medicine 1 , ,","place":["Daejeon, Republic of Korea"]},{"name":"Department of Medical Science, Chungnam National University School of Medicine 2 , ,","place":["Daejeon, Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gyu Min","family":"Lim","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, College of Life Sciences and Biotechnology, Korea University 6 , ,","place":["Seoul, Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dong Wook","family":"Choi","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, College of Life Sciences and Biotechnology, Korea University 6 , ,","place":["Seoul, Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chuna","family":"Kim","sequence":"additional","affiliation":[{"name":"Aging Convergence Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB) 7 , ,","place":["Daejeon, Republic of Korea"]},{"name":"Department of Bioinformatics, KRIBB School of Bioscience, Korea University of Science and Technology 8 , ,","place":["Daejeon, Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yonghoon","family":"Kwon","sequence":"additional","affiliation":[{"name":"Department of Life Sciences, Gwangju Institute of Science and Technology 3 , ,","place":["Gwangju, Republic of Korea"]},{"name":"Integrated Institute of Biomedical Research, Gwangju Institute of Science and Technology 4 , ,","place":["Gwangju, Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3767-1954","authenticated-orcid":true,"given":"Hyon-Seung","family":"Yi","sequence":"additional","affiliation":[{"name":"Laboratory of Endocrinology and Immune System, Chungnam National University School of Medicine 1 , ,","place":["Daejeon, Republic of Korea"]},{"name":"Department of Medical Science, Chungnam National University School of Medicine 2 , ,","place":["Daejeon, Republic of Korea"]},{"name":"Department of Internal Medicine, Chungnam National University School of Medicine 9 , 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