{
  "abstract": "Mitochondria are both a major autophagic substrate and a principal source of signals that control autophagy, yet it is unknown whether a mitochondrial signal can specify which substrate the pathway degrades. Using metformin to inhibit Complex I in human cells, we find that autophagy is redirected rather than induced or suppressed. Inhibition shifts the NAD+/NADH ratio before perturbing the adenylate pool, separating the redox arm of the lesion from the bioenergetic arm. Single-molecule tracking of endogenous ATG13 and WIPI2 shows that initiation is preserved while WIPI2 tethering fails, generating short-lived, abortive autophagosomes; the ULK1 interactome concurrently disengages from cytoskeletal scaffolds, and Parkin-independent mitolysosomes accumulate. This response differs from mTORC1 inhibition and does not require PEN2, and AMPK is engaged non-canonically: 1/2 restrain ATG13 at initiation, while AMPK activation alone does not reproduce the WIPI2 phenotype. Occurring at therapeutic concentrations, these results identify the ULK1 complex as the step at which Complex I inhibition reassigns autophagic substrate.",
  "abstract_shown": true,
  "affiliations": [
    "University of Kansas - Lawrence"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 10,
  "authors": [
    {
      "name": "T. M. Mutawi"
    },
    {
      "name": "S. R. Malvankar"
    },
    {
      "name": "A. Graziani"
    },
    {
      "name": "U. Shah"
    },
    {
      "name": "K. Nguyen"
    },
    {
      "name": "D. G. Broadbent"
    },
    {
      "name": "Z. Clark"
    },
    {
      "name": "M. J. Rekowski"
    },
    {
      "name": "S. M. Lunte"
    },
    {
      "affs": [
        0
      ],
      "name": "C. Barnaba"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/457m3zc2tzd45.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.06.04.730191",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.06.04.730191v2.full",
  "id": "457m3zc2tzd45",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.06.04.730191v2",
  "language": null,
  "licence": "CC-BY-NC",
  "licence_label": "CC BY-NC",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "biorxiv",
      "cell biology"
    ],
    [
      "openalex",
      "2713|Autophagy in Disease and Therapy"
    ]
  ],
  "openalex": "W7163747161",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.06.04.730191v2.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-06-04",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/457m3zc2tzd45.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:26:42Z",
      "native_id": "10.64898/2026.06.04.730191",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.06.04.730191v2"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "biorxiv:cell biology",
      "subfield": "cell-biology"
    }
  ],
  "title": "Complex I Inhibition Redirects Autophagy from Bulk Turnover to Mitochondrial Clearance",
  "title_text": "Complex I Inhibition Redirects Autophagy from Bulk Turnover to Mitochondrial Clearance",
  "type": "preprint",
  "updated_at": "2026-10-30T12:26:42Z",
  "url": "https://research.draconitic.com/paper/457m3zc2tzd45",
  "venue": "bioRxiv",
  "versions": []
}