{
  "abstract": "Mitochondrial function critically dependents on protein quality control systems, with the m -AAA protease plays a key role at the inner mitochondrial membrane (IMM). The evolutionarily conserved prohibitins (PHBs) are essential modulators of this protease across species, yet the molecular mechanisms remain unclear. Here, we present the Cryo-EM structure of the Chaetomium thermophilum PHB ( Ct PHB) complex, revealing a cage-like assembly composed of 11 copies of PHB1/PHB2 heterodimers. Electron microscopic and biochemical analyses suggest that m -AAA proteases are enclosed within the PHB complex through interactions mediated by their SPFH-interacting motif (SIM) exposed in the intermembrane space. Further in situ cryo-ET directly visualizes these cage-protease assemblies in native mitochondria. Disruption of their interface leads to elevated m -AAA protease activity and diminished mitochondrial stress resistance. These data establish PHB complexes as spatial organizers that compartmentalize m -AAA proteases in membrane microdomains to fine tune proteolytic homeostasis. Our findings reveal the critical role of the PHB complex in maintaining mitochondrial proteostasis, providing a unified mechanistic model to explain and reconcile the pleiotropic, and often contradictive phenotypes of PHBs and m -AAA protease in mitochondrial physiology and various disease conditions.",
  "abstract_shown": true,
  "affiliations": [
    "State Key Laboratory of Membrane Biology, Peking-Tsinghua Joint Center for Life Sciences, Academy for Advanced Interdisciplinary Studies, School of Life Sciences, Peking University, Beijing, China",
    "State Key Laboratory of Membrane Biology, Peking-Tsinghua Joint Center for Life Sciences, Academy for Advanced Interdisciplinary Studies, School of Life Sciences, Peking University, Beijing, China. mingaolu@pku.edu.cn",
    "State Key Laboratory of Membrane Biology, Peking-Tsinghua Joint Center for Life Sciences, Academy for Advanced Interdisciplinary Studies, School of Life Sciences, Peking University, Beijing, China. guo.qiang@pku.edu.cn",
    "Beijing Advanced Center of RNA Biology (BEACON), Peking University, Beijing, China. gaon@pku.edu.cn",
    "National Biomedical Imaging Center, Peking University, Beijing, China. gaon@pku.edu.cn",
    "State Key Laboratory of Membrane Biology, Peking-Tsinghua Joint Center for Life Sciences, Academy for Advanced Interdisciplinary Studies, School of Life Sciences, Peking University, Beijing, China. gaon@pku.edu.cn"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 7,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Dingyi Luo"
    },
    {
      "affs": [
        0
      ],
      "name": "Lvqin Zheng",
      "orcid": "0000-0001-8193-841X"
    },
    {
      "affs": [
        1
      ],
      "name": "Ming Lu",
      "orcid": "0009-0000-5809-5442"
    },
    {
      "affs": [
        0
      ],
      "name": "Ziyao Chen"
    },
    {
      "affs": [
        0
      ],
      "name": "P Wang",
      "orcid": "0009-0002-2428-9876"
    },
    {
      "affs": [
        2
      ],
      "name": "Qiang Guo",
      "orcid": "0000-0003-3520-5439"
    },
    {
      "affs": [
        3,
        4,
        5
      ],
      "name": "Ning Gao",
      "orcid": "0000-0003-3067-9993"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/89517zwhv4ej2.bib",
  "cited_by": 10,
  "doi": "10.1038/s41467-026-73040-0",
  "fulltext_url": null,
  "id": "89517zwhv4ej2",
  "issns": [
    "2041-1723"
  ],
  "landing_url": "https://doi.org/10.1038/s41467-026-73040-0",
  "language": "en",
  "licence": "CC-BY-NC-ND",
  "licence_label": "CC BY-NC-ND",
  "licence_source": "journal",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "1312|Mitochondrial Function and Pathology"
    ]
  ],
  "openalex": "W7161065095",
  "pdf_url": null,
  "pmcid": "PMC13376388",
  "pmid": "42129162",
  "published": "2026-05-13",
  "publisher": "Nature Portfolio",
  "ris": "https://research.draconitic.com/paper/89517zwhv4ej2.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T13:26:46Z",
      "native_id": "W7161065095",
      "source": "openalex",
      "url": "https://doi.org/10.1038/s41467-026-73040-0"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "openalex:1312|Mitochondrial Function and Pathology",
      "subfield": "molecular-biology"
    }
  ],
  "title": "Structural basis for prohibitin-mediated regulation of mitochondrial m-AAA protease",
  "title_text": "Structural basis for prohibitin-mediated regulation of mitochondrial m-AAA protease",
  "type": "peer-reviewed",
  "updated_at": "2026-11-06T13:20:30Z",
  "url": "https://research.draconitic.com/paper/89517zwhv4ej2",
  "venue": "Nature Communications",
  "versions": []
}