{
  "abstract": "Mitophagy is a central mitochondrial quality-control pathway, and its pharmacological activation is considered to be geroprotective. However, its small-molecule activators act indirectly by perturbing metabolism or mitochondrial function, limiting selectivity and increasing toxicity. Here, we describe a chemical biology strategy for activating damage-responsive mitophagy using bifunctional small molecules that couple mitochondrial recognition to the recruitment of the autophagic machinery. We designed and synthesized a focused library of chimeric molecules and identified MG-1 as a lead compound. It had minimal effects on basal autophagy but markedly enhanced autophagic flux and mitochondrial clearance under conditions of mitochondrial stress. Biochemical analyses, together with fluorescence and electron microscopy, showed that MG-1 promotes lysosomal degradation of damaged mitochondria without acting as a direct mitochondrial uncoupler. MG-1 was well tolerated across experimental systems and improved locomotor performance in a zebrafish model of MPTP-induced mitochondrial dysfunction. These findings establish damage-gated small-molecule chimeras as a promising approach for selective control of mitochondrial quality.",
  "abstract_shown": true,
  "affiliations": [
    "Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, Moscow, Russia.",
    "Chemical Department, Lomonosov Moscow State University, Moscow, Russia.",
    "Faculty of Fundamental Medicine, M.V. Lomonosov Moscow State University, Moscow, Russia.",
    "Institute of Mitoengineering, Lomonosov Moscow State University, Moscow, Russia.",
    "Pirogov Russian National Research Medical University, Moscow, Russia.",
    "Shemyakin-Ovchinnicov Institute of Bioorganic Chemistry (branch), Russian Academy of Sciences, Pushchino, Russia.",
    "Faculty of Bioengineering and Bioinformatics, Lomonosov Moscow State University, Moscow, Russia.",
    "Moscow Center for Advanced Studies, Moscow, Russia.",
    "Peoples' Friendship University of Russia named After Patrice Lumumba, Moscow, Russia.",
    "Biological Faculty, Lomonosov Moscow State University, Moscow, Russia."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 25,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Ratislav M Ozhiganov"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Ekaterina А Guseva",
      "orcid": "0000-0002-1818-6590"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Alexander Yu Rudenko",
      "orcid": "0000-0002-8320-0539"
    },
    {
      "affs": [
        0
      ],
      "name": "Konstantin G Lyamzaev",
      "orcid": "0000-0001-9921-8031"
    },
    {
      "affs": [
        2
      ],
      "name": "Sofya Y Sokolskaya"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Julia A Golubeva"
    },
    {
      "affs": [
        3
      ],
      "name": "Maria V Belopolskaya",
      "orcid": "0000-0002-6772-2580"
    },
    {
      "affs": [
        0
      ],
      "name": "Nadezda V Andrianova",
      "orcid": "0000-0003-2720-4575"
    },
    {
      "affs": [
        3
      ],
      "name": "Olga V Fadeeva",
      "orcid": "0000-0001-6833-8313"
    },
    {
      "affs": [
        4
      ],
      "name": "Elena О Morgun"
    },
    {
      "affs": [
        5
      ],
      "name": "Elena A Tukhovskaya",
      "orcid": "0000-0001-6174-4052"
    },
    {
      "affs": [
        5
      ],
      "name": "Marina S Kazakova"
    },
    {
      "affs": [
        5
      ],
      "name": "Vladimir M Pavlov",
      "orcid": "0009-0003-8949-5600"
    },
    {
      "affs": [
        6
      ],
      "name": "Daria K Yagoda"
    },
    {
      "affs": [
        7
      ],
      "name": "Elena I Marusich"
    },
    {
      "affs": [
        8
      ],
      "name": "Rose-Lys Zaranaina",
      "orcid": "0009-0000-3444-7351"
    },
    {
      "affs": [
        0
      ],
      "name": "Valeriya B Vays"
    },
    {
      "affs": [
        0
      ],
      "name": "Irina M Vangeli"
    },
    {
      "affs": [
        0
      ],
      "name": "Egor Y Plotnikov",
      "orcid": "0000-0003-2838-3704"
    },
    {
      "affs": [
        3,
        9
      ],
      "name": "Maxim L Lovat"
    },
    {
      "affs": [
        0
      ],
      "name": "Lora E Bakeeva"
    },
    {
      "affs": [
        5
      ],
      "name": "Arkady N Murashev"
    },
    {
      "affs": [
        1
      ],
      "name": "Vladimir I Polshakov",
      "orcid": "0000-0002-3216-5737"
    },
    {
      "affs": [
        0,
        1,
        5
      ],
      "name": "Olga A Dontsova"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Peter V Sergiev",
      "orcid": "0000-0001-8866-1863"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/57axr9t5gybzf.bib",
  "cited_by": 0,
  "doi": "10.1002/advs.78570",
  "fulltext_url": "https://europepmc.org/articles/PMC13720385",
  "id": "57axr9t5gybzf",
  "issns": [
    "2198-3844"
  ],
  "landing_url": "https://europepmc.org/article/MED/42958763",
  "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": [
    [
      "heading",
      "Research Article"
    ],
    [
      "openalex",
      "2713|Autophagy in Disease and Therapy"
    ]
  ],
  "openalex": "W7224903749",
  "pdf_url": "https://europepmc.org/articles/PMC13720385?pdf=render",
  "pmcid": "PMC13720385",
  "pmid": "42958763",
  "published": "2026-10-29",
  "publisher": "Wiley",
  "ris": "https://research.draconitic.com/paper/57axr9t5gybzf.ris",
  "sources": [
    {
      "first_seen": "2026-11-01T00:20:36Z",
      "native_id": "MED:42958763",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42958763"
    },
    {
      "first_seen": "2026-11-03T12:21:16Z",
      "native_id": "PMC13720385",
      "source": "pmc",
      "url": "https://doi.org/10.1002/advs.78570"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2713|Autophagy in Disease and Therapy",
      "subfield": "epidemiology-public-health"
    }
  ],
  "title": "A Damage-Gated Small-Molecule Chimera Selectively Enhances Mitophagy by Coupling Dysfunctional Mitochondria to Autophagy.",
  "title_text": "A Damage-Gated Small-Molecule Chimera Selectively Enhances Mitophagy by Coupling Dysfunctional Mitochondria to Autophagy.",
  "type": "peer-reviewed",
  "updated_at": "2026-11-03T12:21:16Z",
  "url": "https://research.draconitic.com/paper/57axr9t5gybzf",
  "venue": "Advanced science (Weinheim, Baden-Wurttemberg, Germany)",
  "versions": []
}