{
  "abstract": "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-promoting micropeptide), a 29-amino acid peptide encoded by a non-canonical 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 α-ketoglutarate dehydrogenase complex (OGDHc). This interaction modulates OGDHc enzymatic activity, thereby regulating NADH and ATP production. We identified tyrosine-13 as the critical residue mediating the APPM-OGDH 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.",
  "abstract_shown": true,
  "affiliations": [
    "School of Basic Medicine and Forensic Medicine, North Sichuan Medical College, Nanchong, People's Republic of China.",
    "The Engineering Research Center of Synthetic Polypeptide Drug Discovery and Evaluation, China Pharmaceutical University, Nanjing, Jiangsu, People's Republic of China.",
    "Department of Nuclear Medicine, Nanjing First Hospital, Nanjing Medical University, Nanjing, People's Republic of China.",
    "Mudi Meng Honors College, China Pharmaceutical University, Nanjing, People's Republic of China.",
    "State Key Laboratory of Natural Medicines, Ministry of Education, China Pharmaceutical University, Nanjing, People's Republic of China.",
    "Joint International Research Laboratory of Target Discovery and New Drug Innovation, MOE, Nanjing, People's Republic of China."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 10,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Xinqiang Yin",
      "orcid": "0000-0002-4163-3600"
    },
    {
      "affs": [
        1
      ],
      "name": "Weiyan Qi",
      "orcid": "0000-0003-2756-7798"
    },
    {
      "affs": [
        1
      ],
      "name": "Lifen Lin"
    },
    {
      "affs": [
        1
      ],
      "name": "Huilin Zheng"
    },
    {
      "affs": [
        1
      ],
      "name": "Guoxiang Zhao"
    },
    {
      "affs": [
        1
      ],
      "name": "Quan Chen"
    },
    {
      "affs": [
        1,
        2
      ],
      "name": "Guoqiang Shao",
      "orcid": "0000-0002-3277-6933"
    },
    {
      "affs": [
        3
      ],
      "name": "Yifan Wu"
    },
    {
      "affs": [
        1
      ],
      "name": "Jialiang Hu"
    },
    {
      "affs": [
        1,
        4,
        5
      ],
      "name": "Hanmei Xu"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/fhykf7hprn7x8.bib",
  "cited_by": 0,
  "doi": "10.1002/advs.77242",
  "fulltext_url": "https://europepmc.org/articles/PMC13676814",
  "id": "fhykf7hprn7x8",
  "issns": [
    "2198-3844"
  ],
  "landing_url": "https://europepmc.org/article/MED/42893408",
  "language": "eng",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "1312|Mitochondrial Function and Pathology"
    ]
  ],
  "openalex": "W7124218161",
  "pdf_url": "https://europepmc.org/articles/PMC13676814?pdf=render",
  "pmcid": "PMC13676814",
  "pmid": "42893408",
  "published": "2026-10-18",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/fhykf7hprn7x8.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:18:46Z",
      "native_id": "MED:42893408",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42893408"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "openalex:1312|Mitochondrial Function and Pathology",
      "subfield": "molecular-biology"
    }
  ],
  "title": "A Micropeptide Component of the OGDH Complex Modulates ATP Production in the TCA Cycle.",
  "title_text": "A Micropeptide Component of the OGDH Complex Modulates ATP Production in the TCA Cycle.",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:18:46Z",
  "url": "https://research.draconitic.com/paper/fhykf7hprn7x8",
  "venue": "Advanced science (Weinheim, Baden-Wurttemberg, Germany)",
  "versions": []
}