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mitophagy, cells, ambra, pubmed, article, huwe, fig, mitochondrial, google, scholar, phosphorylation, cas, mitochondria, proteins, ikkα, hela, protein, transfected, cell, analysis, central, supplementary, performed, kinase, autophagy, ambramediated, lcb, binding, treated, ubiquitin, interaction, order, mycambraacta, data, nature, antibodies, ambralir, ligase, activity, observed, western, induction, ubiquitylation, degradation, motif, mycambrawt, min, buffer, mfn, blot,

Topics {✒️}

nature portfolio privacy policy myc-ambra1wt-expressing sh-sy5y cells advertising mt-mkeima-expressing pink1 knockout mt-mkeima expressing wild-type preventing c-myc/miz1-mediated proto-oncogene c-myc regulation bnip3l/nix-mediated mitophagy protects german research foundation regulate pink1/parkin-independent mitophagy pink1/parkin-related mitophagy receptors index lam-bighi grant initiative reprints ha-ikkαk44m-expressing hela cells pink1/parkin-dependent mitophagy pathway p-s1014-ambra1 antibody generation transcription factor nf-κb mt-mkeima fluorescence intensity mito-aggresome-positive transfected cells nature 524 nature 454 nature 472 nature 392 nature mule/arf-bp1 mt-mkeima-pink1-ko mt-mkeima pink1-ko isotope labelling media ha-ikkαk44m kinase-dead mutant park6-linked parkinsonism occurs mitochondrial research nf-κb-independent manner canonical pink1/parkin-dependent author information authors anti-p-s1014-ambra1 antibody ck2α-disturbed mitochondrial homeostasis kinase-dead ip-ikkαk44m sample pink1 phospho-ubiquitin signals myc-ambra1acta strongly favours cargo receptor-mediated autophagy11 sh-sy5y cells transfected sh-sy5y cells exposed ip-ha-ikkαk44m final pellets pink1/parkin-independent mitophagy13 ambra1-bcl2-family proteins relationship pink1/parkin-mediated mitophagy13 anti-apoptotic factor mcl1 research conducted

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• How robust are protein folding simulations with respect to force field parameterization?

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      headline:HUWE1 E3 ligase promotes PINK1/PARKIN-independent mitophagy by regulating AMBRA1 activation via IKKα
      description:The selective removal of undesired or damaged mitochondria by autophagy, known as mitophagy, is crucial for cellular homoeostasis, and prevents tumour diffusion, neurodegeneration and ageing. The pro-autophagic molecule AMBRA1 (autophagy/beclin-1 regulator-1) has been defined as a novel regulator of mitophagy in both PINK1/PARKIN-dependent and -independent systems. Here, we identified the E3 ubiquitin ligase HUWE1 as a key inducing factor in AMBRA1-mediated mitophagy, a process that takes place independently of the main mitophagy receptors. Furthermore, we show that mitophagy function of AMBRA1 is post-translationally controlled, upon HUWE1 activity, by a positive phosphorylation on its serine 1014. This modification is mediated by the IKKα kinase and induces structural changes in AMBRA1, thus promoting its interaction with LC3/GABARAP (mATG8) proteins and its mitophagic activity. Altogether, these results demonstrate that AMBRA1 regulates mitophagy through a novel pathway, in which HUWE1 and IKKα are key factors, shedding new lights on the regulation of mitochondrial quality control and homoeostasis in mammalian cells. Mitophagy is crucial for mitochondrial quality control and maintenance of cellular homeostasis. Here the authors identify an E3 ubiquitin ligase, HUWE1, that collaborates with LC3-interacting protein AMBRA1 to induce mitochondrial clearance.
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            address:
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      name:Francesco Cecconi
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            address:
               name:Department of Biology, University of Rome Tor Vergata, Rome, Italy
               type:PostalAddress
            type:Organization
            name:IRCCS Bambino Gesù Children’s Hospital
            address:
               name:Department of Paediatric Haematology, Oncology and Cell and Gene Therapy, IRCCS Bambino Gesù Children’s Hospital, Rome, Italy
               type:PostalAddress
            type:Organization
            name:Danish Cancer Society Research Center
            address:
               name:Unit of Cell Stress and Survival, Danish Cancer Society Research Center, Copenhagen, Denmark
               type:PostalAddress
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      email:[email protected]
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      name:Department of Paediatric Haematology, Oncology and Cell and Gene Therapy, IRCCS Bambino Gesù Children’s Hospital, Rome, Italy
      name:IRCCS FONDAZIONE SANTA LUCIA, Rome, Italy
      name:National Research Council of Italy (CNR), Institute of Translational Pharmacology IFT, Rome, Italy
      name:Department of Paediatric Haematology, Oncology and Cell and Gene Therapy, IRCCS Bambino Gesù Children’s Hospital, Rome, Italy
      name:Department of Biology, University of Rome Tor Vergata, Rome, Italy
      name:IRCCS- Regina Elena, National Cancer Institute, Rome, Italy
      name:Department of Biology, University of Fribourg, Fribourg, Switzerland
      name:Institute of Biophysical and Center for Biomolecular Magnetic Resonance, Goethe University, Frankfurt, Germany
      name:Computational Biology Laboratory, Danish Cancer Society Research Center, 2100 Copenhagen, Denmark
      name:Computational Biology Laboratory, Danish Cancer Society Research Center, 2100 Copenhagen, Denmark
      name:Department of Experimental Medicine and Surgery, University of Rome Tor Vergata, Rome, Italy
      name:Computational Biology Laboratory, Danish Cancer Society Research Center, 2100 Copenhagen, Denmark
      name:Department of Biology, University of Fribourg, Fribourg, Switzerland
      name:Covalab, Villeurbanne, France
      name:IRCCS- Regina Elena, National Cancer Institute, Rome, Italy
      name:Department of Comparative Biomedical Sciences, Royal Veterinary College, London, UK
      name:University College London Consortium for Mitochondrial Research, University College London, London, UK
      name:Institute of Biophysical and Center for Biomolecular Magnetic Resonance, Goethe University, Frankfurt, Germany
      name:Institute of Biophysical and Center for Biomolecular Magnetic Resonance, Goethe University, Frankfurt, Germany
      name:Department of Biology, University of Rome Tor Vergata, Rome, Italy
      name:IRCCS FONDAZIONE SANTA LUCIA, Rome, Italy
      name:Department of Biology, University of Rome Tor Vergata, Rome, Italy
      name:Department of Paediatric Haematology, Oncology and Cell and Gene Therapy, IRCCS Bambino Gesù Children’s Hospital, Rome, Italy
      name:Unit of Cell Stress and Survival, Danish Cancer Society Research Center, Copenhagen, Denmark

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