{
  "abstract": "Intrahepatic cholestasis of pregnancy (ICP) is a gestational liver disorder characterized by impaired placental vascular architecture, leading to placental dysfunction and fetal growth restriction. Our prior work demonstrated that the transcription repressor BACH1 modulates SLC25A51 expression to regulate placental injury under ICP conditions. MOTS-c, a mitochondria-originated peptide, participates in vascular homeostasis, yet its biological functions within the placental vasculature during ICP have not been fully characterized. Clinical analyses revealed significantly reduced MOTS-c protein levels in both maternal serum and placental tissues from ICP patients. In a cholic acid-induced murine model of ICP, MOTS-c administration promoted placental angiogenesis and inhibited apoptosis of placental vascular endothelial cells. These protective effects were recapitulated in vitro, where MOTS-c attenuated oxidative stress and apoptosis in human umbilical vein endothelial cells (HUVECs) exposed to taurocholic acid. Mechanistically, biotinylated MOTS-c pull-down coupled with mass spectrometry identified BACH1 as a direct binding partner; subsequent functional validation demonstrated that MOTS-c binds competitively to the D560 residue of BACH1, thereby displacing the deubiquitinase USP7 and promoting K33-linked polyubiquitination and proteasomal degradation of BACH1. Consequently, MOTS-c-mediated BACH1 depletion relieves transcriptional repression of SLC25A51, enhancing mitochondrial NAD+ import, biogenesis, and redox resilience. Importantly, BACH1 overexpression abolished MOTS-c–induced protection in HUVECs, confirming the functional dependency of MOTS-c on this axis. In vivo, MOTS-c treatment in CA-induced ICP mice significantly improved key offspring developmental parameters-including birth weight, placental efficiency, and neonatal survival. Collectively, these findings establish MOTS-c as a placenta-targeted endogenous regulator that ameliorates ICP-associated placental vascular pathology and adverse perinatal outcomes via modulation of the BACH1/SLC25A51 signaling axis.\n\nSupplementary Information: The online version contains supplementary material available at https://doi.org/10.1186/s12964-026-03109-2.",
  "abstract_shown": true,
  "affiliations": [
    "Wuxi School of Medicine, Jiangnan University, No.1800 Lihu Avenue, Wuxi, Jiangsu province 214122 PR China",
    "Medical Basic Research Innovation Center for Gut Microbiota and Chronic Diseases, Ministry of Education, Jiangnan University, 1800 Lihu Avenue, Wuxi, Jiangsu province 214122 People’s Republic of China",
    "Department of Obstetrics, Maternity and Child Health Care Affiliated Hospital, Jiaxing University, No.2468 East Central Road, South Lake District, Jiaxing, Zhejiang province 314000 People’s Republic of China",
    "Department of Respiratory and Critical Care Medicine, Jiangnan University Medical Center, 68 Zhongshan Road, Wuxi, Jiangsu Province 2140002 People’s Republic of China",
    "Laboratory Medicine Center, Taihu General Hospital, Suzhou Municipal Hospital, 80 Tian’edang Road, Wuzhong District, Suzhou, Jiangsu Province 215104 People’s Republic of China"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 13,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Shengpeng Li"
    },
    {
      "affs": [
        2
      ],
      "name": "Ling Ai"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Longlong Ge"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Dan Chen"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Shiqi Chen"
    },
    {
      "affs": [
        0,
        1,
        3
      ],
      "name": "Wenlong Zhang"
    },
    {
      "affs": [
        4
      ],
      "name": "Yanli Zhang"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Jiaojiao Sun"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Yijing Chen"
    },
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "Yaxian Wu"
    },
    {
      "affs": [
        2
      ],
      "name": "Weiying Zhu"
    },
    {
      "affs": [
        0,
        1,
        3
      ],
      "name": "Shuguang Han"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Qingfeng Pang"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/2dq350bajnxqa.bib",
  "cited_by": 0,
  "doi": "10.1186/s12964-026-03109-2",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13711938/",
  "id": "2dq350bajnxqa",
  "issns": [
    "1478-811X"
  ],
  "landing_url": "https://doi.org/10.1186/s12964-026-03109-2",
  "language": "en",
  "licence": "CC-BY-NC-ND-4.0",
  "licence_label": "CC BY-NC-ND 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Research"
    ],
    [
      "openalex",
      "2729|Pregnancy and preeclampsia studies"
    ]
  ],
  "openalex": "W7171658305",
  "pdf_url": null,
  "pmcid": "PMC13711938",
  "pmid": "42934731",
  "published": "2026-07-29",
  "publisher": "BMC",
  "ris": "https://research.draconitic.com/paper/2dq350bajnxqa.ris",
  "sources": [
    {
      "first_seen": "2026-10-31T12:22:37Z",
      "native_id": "PMC13711938",
      "source": "pmc",
      "url": "https://doi.org/10.1186/s12964-026-03109-2"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2729|Pregnancy and preeclampsia studies",
      "subfield": "reproductive-child"
    }
  ],
  "title": "MOTS-c attenuates placental vascular endothelial cell apoptosis in intrahepatic cholestasis of pregnancy by inhibiting K33-linked deubiquitination of BACH1",
  "title_text": "MOTS-c attenuates placental vascular endothelial cell apoptosis in intrahepatic cholestasis of pregnancy by inhibiting K33-linked deubiquitination of BACH1",
  "type": "peer-reviewed",
  "updated_at": "2026-10-31T12:22:37Z",
  "url": "https://research.draconitic.com/paper/2dq350bajnxqa",
  "venue": "Cell Communication and Signaling : CCS",
  "versions": []
}