{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,18]],"date-time":"2026-10-18T12:43:54Z","timestamp":1792327434138,"version":"4.4.0"},"reference-count":44,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,10,18]],"date-time":"2026-10-18T00:00:00Z","timestamp":1792281600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,10,18]],"date-time":"2026-10-18T00:00:00Z","timestamp":1792281600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["advanced.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Advanced Science"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Since its elucidation, the tricarboxylic acid (TCA) cycle has been regarded as a fully defined enzymatic pathway. Here, we report the discovery of a previously unrecognized micropeptide component of this central metabolic system. Through analyzing ribosome profiling data from the mouse sORFs.org database, we discovered APPM (ATP production\u2013promoting micropeptide), a 29\u2013amino acid peptide encoded by a non\u2010canonical small open reading frame within the mouse Ctsb gene. APPM localizes to the mitochondrial matrix and inner membrane, where it directly binds to the E1 subunit (OGDH) of the \u03b1\u2010ketoglutarate dehydrogenase complex (OGDHc). This interaction modulates OGDHc enzymatic activity, thereby regulating NADH and ATP production. We identified tyrosine\u201013 as the critical residue mediating the APPM\u2010OGDH interaction and functional activation. Exogenous APPM administration increased ATP levels in vivo and, in a mouse model of heart failure, restored cardiac function, outperforming the reference drug trimetazidine. Collectively, our findings identify APPM as the first micropeptide regulator of the OGDH complex, expanding the known repertoire of the TCA cycle and presenting a potential therapeutic strategy for diseases characterized by bioenergetic insufficiency.<\/jats:p>","DOI":"10.1002\/advs.77242","type":"journal-article","created":{"date-parts":[[2026,10,18]],"date-time":"2026-10-18T12:11:51Z","timestamp":1792325511000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A Micropeptide Component of the OGDH Complex Modulates ATP Production in the TCA Cycle"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4163-3600","authenticated-orcid":false,"given":"Xinqiang","family":"Yin","sequence":"first","affiliation":[{"name":"School of Basic Medicine and Forensic Medicine North Sichuan Medical College  Nanchong People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2756-7798","authenticated-orcid":false,"given":"Weiyan","family":"Qi","sequence":"additional","affiliation":[{"name":"The Engineering Research Center of Synthetic Polypeptide Drug Discovery and Evaluation China Pharmaceutical University  Nanjing Jiangsu People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lifen","family":"Lin","sequence":"additional","affiliation":[{"name":"The Engineering Research Center of Synthetic Polypeptide Drug Discovery and Evaluation China Pharmaceutical University  Nanjing Jiangsu People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huilin","family":"Zheng","sequence":"additional","affiliation":[{"name":"The Engineering Research Center of Synthetic Polypeptide Drug Discovery and Evaluation China Pharmaceutical University  Nanjing Jiangsu People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guoxiang","family":"Zhao","sequence":"additional","affiliation":[{"name":"The Engineering Research Center of Synthetic Polypeptide Drug Discovery and Evaluation China Pharmaceutical University  Nanjing Jiangsu People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Quan","family":"Chen","sequence":"additional","affiliation":[{"name":"The Engineering Research Center of Synthetic Polypeptide Drug Discovery and Evaluation China Pharmaceutical University  Nanjing Jiangsu People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3277-6933","authenticated-orcid":false,"given":"Guoqiang","family":"Shao","sequence":"additional","affiliation":[{"name":"The Engineering Research Center of Synthetic Polypeptide Drug Discovery and Evaluation China Pharmaceutical University  Nanjing Jiangsu People's Republic of 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Natural Medicines Ministry of Education China Pharmaceutical University  Nanjing People's Republic of China"},{"name":"Joint International Research Laboratory of Target Discovery and New Drug Innovation MOE  Nanjing People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,10,18]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/s42255-023-00838-3"},{"key":"e_1_2_10_3_1","doi-asserted-by":"crossref","first-page":"161","DOI":"10.3892\/mmr.2020.11800","article-title":"Mitochondrial Proteomics Alterations in Rat Hearts Following Ischemia\/Reperfusion and Diazoxide Post\u2011Conditioning","volume":"23","author":"Pan Y.","year":"2021","journal-title":"Molecular Medicine 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