{
  "abstract": "Excessive secretion of mineralocorticoid aldosterone (ALD) and overactivation of mineralocorticoid receptor (MR) are considered major drivers of cardiac remodeling and heart failure in patients with primary aldosteronism. Cuproptosis is a copper-dependent form of regulated cell death that has been implicated in pathological cardiac remodeling. However, its mechanism in ALD/MR-induced cardiac remodeling remains unclear. In this study, it is found that ALD-induced cardiac remodeling is accompanied by copper overload and cuproptosis-associated mitochondrial proteotoxic stress. Kelch like family member 20 (KLHL20) functions as a substrate adaptor of the Cullin3 (CUL3) ubiquitin ligase complex. Its expression is significantly decreased in ALD-stimulated myocardium. Cardiomyocyte-specific knockout of KLHL20 aggravates ALD-induced cuproptosis, myocardial hypertrophy, and interstitial fibrosis. Concurrent treatment with the copper chelator tetrathiomolybdate (TTM) attenuates these aggravated pathological changes. Mechanistically, KLHL20 promotes polyubiquitination and subsequent proteasomal degradation of MR, thereby limiting MR protein accumulation and nuclear localization. Consequently, MR-dependent transcription of the copper transporter Solute carrier family 31 member 1 (SLC31A1) is suppressed. As a result, cardiomyocyte copper overload and mitochondrial proteotoxic stress are alleviated. However, sustained ALD stimulation downregulates KLHL20 expression, thereby weakening KLHL20-mediated control of MR protein stability. Cardiomyocyte-specific overexpression of KLHL20 significantly attenuates cardiac remodeling. These findings indicate that KLHL20 is a clinically viable therapeutic target for combating cardiac remodeling.",
  "abstract_shown": true,
  "affiliations": [
    "State Key Laboratory for Innovation and Transformation of Luobing Theory, Key Laboratory of Cardiovascular Remodeling and Function Research of MOE, NHC, CAMS and Shandong Province, Department of Cardiology, Qilu Hospital of Shandong University, Jinan, 250012, China"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 12,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Jinghan Hai"
    },
    {
      "affs": [
        0
      ],
      "name": "Huaitao Yu"
    },
    {
      "affs": [
        0
      ],
      "name": "Yang Hu"
    },
    {
      "affs": [
        0
      ],
      "name": "Yuan Zhao"
    },
    {
      "affs": [
        0
      ],
      "name": "Panpan Xu"
    },
    {
      "affs": [
        0
      ],
      "name": "Xiangping Ma"
    },
    {
      "affs": [
        0
      ],
      "name": "Xuehui Zheng"
    },
    {
      "affs": [
        0
      ],
      "name": "Jingyuan Li"
    },
    {
      "affs": [
        0
      ],
      "name": "Jing Liu"
    },
    {
      "affs": [
        0
      ],
      "name": "Xiaofan Han"
    },
    {
      "affs": [
        0
      ],
      "name": "Yun Ti"
    },
    {
      "affs": [
        0
      ],
      "name": "Peili Bu"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/36n8jfz7nrnba.bib",
  "cited_by": 0,
  "doi": "10.1016/j.redox.2026.104442",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13742509/",
  "id": "36n8jfz7nrnba",
  "issns": [
    "2213-2317"
  ],
  "landing_url": "https://doi.org/10.1016/j.redox.2026.104442",
  "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 Paper"
    ],
    [
      "openalex",
      "2712|Hormonal Regulation and Hypertension"
    ]
  ],
  "openalex": "W7223241482",
  "pdf_url": null,
  "pmcid": "PMC13742509",
  "pmid": "42945624",
  "published": "2026-10-22",
  "publisher": "Elsevier",
  "ris": "https://research.draconitic.com/paper/36n8jfz7nrnba.ris",
  "sources": [
    {
      "first_seen": "2026-11-10T12:23:20Z",
      "native_id": "PMC13742509",
      "source": "pmc",
      "url": "https://doi.org/10.1016/j.redox.2026.104442"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2712|Hormonal Regulation and Hypertension",
      "subfield": "endocrinology-metabolism"
    }
  ],
  "title": "KLHL20 protects against aldosterone-induced cardiomyocyte cuproptosis by promoting ubiquitination-mediated MR degradation",
  "title_text": "KLHL20 protects against aldosterone-induced cardiomyocyte cuproptosis by promoting ubiquitination-mediated MR degradation",
  "type": "peer-reviewed",
  "updated_at": "2026-11-10T12:23:20Z",
  "url": "https://research.draconitic.com/paper/36n8jfz7nrnba",
  "venue": "Redox Biology",
  "versions": []
}