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ATPase activity of DFCP1 controls selective autophagy

Nahse, Viola (författare)
Univ Oslo, Fac Med, Ctr Canc Cell Reprogramming, N-0379 Montebello, Oslo, Norway.;Oslo Univ Hosp, Inst Canc Res, Dept Mol Cell Biol, N-0379 Montebello, Oslo, Norway.;Univ Helsinki, Fac Med, Dept Anat, Helsinki, Finland.;Univ Helsinki, Fac Med, Stem Cells & Metab Res Program, Helsinki, Finland.
Raiborg, Camilla (författare)
Univ Oslo, Fac Med, Ctr Canc Cell Reprogramming, N-0379 Montebello, Oslo, Norway.;Oslo Univ Hosp, Inst Canc Res, Dept Mol Cell Biol, N-0379 Montebello, Oslo, Norway.
Tan, Kia Wee (författare)
Uppsala universitet,Institutionen för medicinsk cellbiologi,Univ Oslo, Fac Med, Ctr Canc Cell Reprogramming, N-0379 Montebello, Oslo, Norway.;Oslo Univ Hosp, Inst Canc Res, Dept Mol Cell Biol, N-0379 Montebello, Oslo, Norway
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Mork, Sissel (författare)
Univ Oslo, Fac Med, Ctr Canc Cell Reprogramming, N-0379 Montebello, Oslo, Norway.;Oslo Univ Hosp, Inst Canc Res, Dept Mol Cell Biol, N-0379 Montebello, Oslo, Norway.
Torgersen, Maria Lyngaas (författare)
Univ Oslo, Fac Med, Ctr Canc Cell Reprogramming, N-0379 Montebello, Oslo, Norway.;Oslo Univ Hosp, Inst Canc Res, Dept Mol Cell Biol, N-0379 Montebello, Oslo, Norway.
Wenzel, Eva Maria (författare)
Univ Oslo, Fac Med, Ctr Canc Cell Reprogramming, N-0379 Montebello, Oslo, Norway.;Oslo Univ Hosp, Inst Canc Res, Dept Mol Cell Biol, N-0379 Montebello, Oslo, Norway.
Nager, Mireia (författare)
Univ Tromso Arctic Univ Norway, Dept Med Biol, Autophagy Res Grp, Tromso, Norway.
Salo, Veijo T. T. (författare)
Univ Helsinki, Fac Med, Dept Anat, Helsinki, Finland.;Univ Helsinki, Fac Med, Stem Cells & Metab Res Program, Helsinki, Finland.;European Mol Biol Lab, Struct & Computat Biol Unit, Heidelberg, Germany.
Johansen, Terje (författare)
Ikonen, Elina (författare)
Univ Helsinki, Fac Med, Dept Anat, Helsinki, Finland.;Univ Helsinki, Fac Med, Stem Cells & Metab Res Program, Helsinki, Finland.
Schink, Kay Oliver (författare)
Univ Oslo, Fac Med, Ctr Canc Cell Reprogramming, N-0379 Montebello, Oslo, Norway.;Oslo Univ Hosp, Inst Canc Res, Dept Mol Cell Biol, N-0379 Montebello, Oslo, Norway.;Univ Oslo, Inst Basic Med Sci, Dept Mol Med, POB 1112 Blindern, N-0317 Oslo, Norway.
Stenmark, Harald (författare)
Univ Oslo, Fac Med, Ctr Canc Cell Reprogramming, N-0379 Montebello, Oslo, Norway.;Oslo Univ Hosp, Inst Canc Res, Dept Mol Cell Biol, N-0379 Montebello, Oslo, Norway.
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Univ Oslo, Fac Med, Ctr Canc Cell Reprogramming, N-0379 Montebello, Oslo, Norway;Oslo Univ Hosp, Inst Canc Res, Dept Mol Cell Biol, N-0379 Montebello, Oslo, Norway.;Univ Helsinki, Fac Med, Dept Anat, Helsinki, Finland.;Univ Helsinki, Fac Med, Stem Cells & Metab Res Program, Helsinki, Finland. Univ Oslo, Fac Med, Ctr Canc Cell Reprogramming, N-0379 Montebello, Oslo, Norway.;Oslo Univ Hosp, Inst Canc Res, Dept Mol Cell Biol, N-0379 Montebello, Oslo, Norway. (creator_code:org_t)
Springer Nature, 2023
2023
Engelska.
Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 14:1
Relaterad länk:
https://doi.org/10.1...
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https://uu.diva-port... (primary) (Raw object)
https://urn.kb.se/re...
https://doi.org/10.1...
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  • Tidskriftsartikel (refereegranskat)
Abstract Ämnesord
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  • The endoplasmic reticulum protein DFCP1 is found on omegasomes implicated in autophagosome biogenesis, but its function has remained unknown. Here, Nahse et al. show that DFCP1 is an ATPase that mediates selective autophagy by promoting constriction of large omegasomes. Cellular homeostasis is governed by removal of damaged organelles and protein aggregates by selective autophagy mediated by cargo adaptors such as p62/SQSTM1. Autophagosomes can assemble in specialized cup-shaped regions of the endoplasmic reticulum (ER) known as omegasomes, which are characterized by the presence of the ER protein DFCP1/ZFYVE1. The function of DFCP1 is unknown, as are the mechanisms of omegasome formation and constriction. Here, we demonstrate that DFCP1 is an ATPase that is activated by membrane binding and dimerizes in an ATP-dependent fashion. Whereas depletion of DFCP1 has a minor effect on bulk autophagic flux, DFCP1 is required to maintain the autophagic flux of p62 under both fed and starved conditions, and this is dependent on its ability to bind and hydrolyse ATP. While DFCP1 mutants defective in ATP binding or hydrolysis localize to forming omegasomes, these omegasomes fail to constrict properly in a size-dependent manner. Consequently, the release of nascent autophagosomes from large omegasomes is markedly delayed. While knockout of DFCP1 does not affect bulk autophagy, it inhibits selective autophagy, including aggrephagy, mitophagy and micronucleophagy. We conclude that DFCP1 mediates ATPase-driven constriction of large omegasomes to release autophagosomes for selective autophagy.

Ämnesord

NATURVETENSKAP  -- Biologi -- Biokemi och molekylärbiologi (hsv//swe)
NATURAL SCIENCES  -- Biological Sciences -- Biochemistry and Molecular Biology (hsv//eng)
MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)
MEDICIN OCH HÄLSOVETENSKAP  -- Medicinsk bioteknologi -- Medicinsk bioteknologi (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Medical Biotechnology -- Medical Biotechnology (hsv//eng)

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