A quantitative ultrastructural timeline of nuclear autophagy reveals a role for dynamin-like protein 1 at the nuclear envelope.

Autor:	Mannino PJ; Department of Cell Biology, Yale School of Medicine, 295 Congress Ave, New Haven, CT, 06520., Perun A; Department of Cell Biology, Yale School of Medicine, 295 Congress Ave, New Haven, CT, 06520., Surovstev I; Department of Cell Biology, Yale School of Medicine, 295 Congress Ave, New Haven, CT, 06520.; Department of Physics, Yale University, New Haven, CT, 06511., Ader NR; Department of Cell Biology, Yale School of Medicine, 295 Congress Ave, New Haven, CT, 06520., Shao L; Department of Cell Biology, Yale School of Medicine, 295 Congress Ave, New Haven, CT, 06520., Melia TJ; Department of Cell Biology, Yale School of Medicine, 295 Congress Ave, New Haven, CT, 06520., King MC; Department of Cell Biology, Yale School of Medicine, 295 Congress Ave, New Haven, CT, 06520.; Department of Molecular Cellular and Developmental Biology, Yale University, New Haven, CT, 06511., Lusk CP; Department of Cell Biology, Yale School of Medicine, 295 Congress Ave, New Haven, CT, 06520.
Jazyk:	angličtina
Zdroj:	BioRxiv : the preprint server for biology [bioRxiv] 2024 Feb 15. Date of Electronic Publication: 2024 Feb 15.
DOI:	10.1101/2024.02.14.580336
Abstrakt:	Autophagic mechanisms that maintain nuclear envelope homeostasis are bulwarks to aging and disease. By leveraging 4D lattice light sheet microscopy and correlative light and electron tomography, we define a quantitative and ultrastructural timeline of a nuclear macroautophagy (nucleophagy) pathway in yeast. Nucleophagy initiates with a rapid local accumulation of the nuclear cargo adaptor Atg39 at the nuclear envelope adjacent to the nucleus-vacuole junction and is delivered to the vacuole in ~300 seconds through an autophagosome intermediate. Mechanistically, nucleophagy incorporates two consecutive and genetically defined membrane fission steps: inner nuclear membrane (INM) fission generates a lumenal vesicle in the perinuclear space followed by outer nuclear membrane (ONM) fission to liberate a double membraned vesicle to the cytosol. ONM fission occurs independently of phagophore engagement and instead relies surprisingly on dynamin-like protein1 (Dnm1), which is recruited to sites of Atg39 accumulation at the nuclear envelope. Loss of Dnm1 compromises nucleophagic flux by stalling nucleophagy after INM fission. Our findings reveal how nuclear and INM cargo are removed from an intact nucleus without compromising its integrity, achieved in part by a non-canonical role for Dnm1 in nuclear envelope remodeling.
Databáze:	MEDLINE
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