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DGAT1 activity sync...
DGAT1 activity synchronises with mitophagy to protect cells from metabolic rewiring by iron depletion
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- Long, Maeve (författare)
- Translational Stem Cell Biology & Metabolism Program, Research Programs Unit, Faculty of Medicine, Biomedicum Helsinki, University of Helsinki, Helsinki, Finland; Science for Life Laboratory, Department of Oncology and Pathology, Karolinska Institutet, Stockholm, Sweden
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- Sanchez-Martinez, Alvaro (författare)
- MRC Mitochondrial Biology Unit, University of Cambridge, Cambridge, United Kingdom
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- Longo, Marianna (författare)
- MRC Protein Phosphorylation & Ubiquitylation Unit, School of Life Sciences, The Sir James Black Centre, University of Dundee, Dundee, United Kingdom
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- Suomi, Fumi (författare)
- Translational Stem Cell Biology & Metabolism Program, Research Programs Unit, Faculty of Medicine, Biomedicum Helsinki, University of Helsinki, Helsinki, Finland
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- Stenlund, Hans (författare)
- Umeå universitet,Institutionen för fysiologisk botanik,Swedish Metabolomics Centre
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- Johansson, Annika I. (författare)
- Umeå universitet,Institutionen för fysiologisk botanik,Swedish Metabolomics Centre
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- Ehsan, Homa (författare)
- Translational Stem Cell Biology & Metabolism Program, Research Programs Unit, Faculty of Medicine, Biomedicum Helsinki, University of Helsinki, Helsinki, Finland
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- Salo, Veijo T. (författare)
- Translational Stem Cell Biology & Metabolism Program, Research Programs Unit, Faculty of Medicine, Biomedicum Helsinki, University of Helsinki, Helsinki, Finland; Department of Anatomy, Faculty of Medicine, Biomedicum Helsinki, University of Helsinki, Helsinki, Finland; Minerva Foundation Institute for Medical Research, Helsinki, Finland; Structural and Computational Biology Unit, European Molecular Biology Laboratory, Heidelberg, Germany
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- Montava-Garriga, Lambert (författare)
- MRC Protein Phosphorylation & Ubiquitylation Unit, School of Life Sciences, The Sir James Black Centre, University of Dundee, Dundee, United Kingdom; Discovery Biology, Discovery Sciences, R&D, AstraZeneca, Cambridge, United Kingdom
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- Naddafi, Seyedehshima (författare)
- Translational Stem Cell Biology & Metabolism Program, Research Programs Unit, Faculty of Medicine, Biomedicum Helsinki, University of Helsinki, Helsinki, Finland
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- Ikonen, Elina (författare)
- Translational Stem Cell Biology & Metabolism Program, Research Programs Unit, Faculty of Medicine, Biomedicum Helsinki, University of Helsinki, Helsinki, Finland; Department of Anatomy, Faculty of Medicine, Biomedicum Helsinki, University of Helsinki, Helsinki, Finland; Minerva Foundation Institute for Medical Research, Helsinki, Finland
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- Ganley, Ian G. (författare)
- MRC Protein Phosphorylation & Ubiquitylation Unit, School of Life Sciences, The Sir James Black Centre, University of Dundee, Dundee, United Kingdom
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- Whitworth, Alexander J. (författare)
- MRC Mitochondrial Biology Unit, University of Cambridge, Cambridge, United Kingdom
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- McWilliams, Thomas G. (författare)
- Translational Stem Cell Biology & Metabolism Program, Research Programs Unit, Faculty of Medicine, Biomedicum Helsinki, University of Helsinki, Helsinki, Finland; Department of Anatomy, Faculty of Medicine, Biomedicum Helsinki, University of Helsinki, Helsinki, Finland
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(creator_code:org_t)
- 2022-04-12
- 2022
- Engelska.
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Ingår i: EMBO Journal. - : John Wiley & Sons. - 0261-4189 .- 1460-2075. ; 41
- Relaterad länk:
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https://doi.org/10.1...
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https://umu.diva-por... (primary) (Raw object)
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https://urn.kb.se/re...
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https://doi.org/10.1...
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http://kipublication...
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Abstract
Ämnesord
Stäng
- Mitophagy removes defective mitochondria via lysosomal elimination. Increased mitophagy coincides with metabolic reprogramming, yet it remains unknown whether mitophagy is a cause or consequence of such state changes. The signalling pathways that integrate with mitophagy to sustain cell and tissue integrity also remain poorly defined. We performed temporal metabolomics on mammalian cells treated with deferiprone, a therapeutic iron chelator that stimulates PINK1/PARKIN-independent mitophagy. Iron depletion profoundly rewired the metabolome, hallmarked by remodelling of lipid metabolism within minutes of treatment. DGAT1-dependent lipid droplet biosynthesis occurred several hours before mitochondrial clearance, with lipid droplets bordering mitochondria upon iron chelation. We demonstrate that DGAT1 inhibition restricts mitophagy in vitro, with impaired lysosomal homeostasis and cell viability. Importantly, genetic depletion of DGAT1 in vivo significantly impaired neuronal mitophagy and locomotor function in Drosophila. Our data define iron depletion as a potent signal that rapidly reshapes metabolism and establishes an unexpected synergy between lipid homeostasis and mitophagy that safeguards cell and tissue integrity.
Ämnesord
- NATURVETENSKAP -- Biologi -- Cellbiologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Cell Biology (hsv//eng)
Nyckelord
- DGAT1
- iron
- lipid droplet
- metabolism
- mitophagy
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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Till lärosätets databas
- Av författaren/redakt...
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Long, Maeve
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Sanchez-Martinez ...
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Longo, Marianna
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Suomi, Fumi
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Stenlund, Hans
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Johansson, Annik ...
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Ehsan, Homa
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Salo, Veijo T.
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Montava-Garriga, ...
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Naddafi, Seyedeh ...
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Ikonen, Elina
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Ganley, Ian G.
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Whitworth, Alexa ...
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McWilliams, Thom ...
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- NATURVETENSKAP
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NATURVETENSKAP
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och Biologi
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och Cellbiologi
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EMBO Journal
- Av lärosätet
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Umeå universitet
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Karolinska Institutet