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Nagakannan, P.* ; Islam, M.I.* ; Conrad, M. ; Eftekharpour, E.*

Cathepsin B is an executioner of ferroptosis.

Biochim. Biophys. Acta-Mol. Cell Res. 1868:118928 (2021)
Verlagsversion DOI PMC
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Open Access Green möglich sobald Postprint bei der ZB eingereicht worden ist.
Ferroptosis is a necrotic form of cell death caused by inactivation of the glutathione system and uncontrolled iron-mediated lipid peroxidation. Increasing evidence implicates ferroptosis in a wide range of diseases from neurotrauma to cancer, highlighting the importance of identifying an executioner system that can be exploited for clinical applications. In this study, using pharmacological and genetic models of ferroptosis, we observed that lysosomal membrane permeabilization and cytoplasmic leakage of cathepsin B unleashes structural and functional changes in mitochondria and promotes a not previously reported cleavage of histone H3. Inhibition of cathepsin-B robustly rescued cellular membrane integrity and chromatin degradation. We show that these protective effects are independent of glutathione peroxidase-4 and are mediated by preventing lysosomal membrane damage. This was further confirmed when cathepsin B knockout primary fibroblasts remained unaffected in response to various ferroptosis inducers. Our work identifies new and yet-unrecognized aspects of ferroptosis and identifies cathepsin B as a mediator of ferroptotic cell death.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Autophagy ; Glutathione ; Gpx4 ; Histone H3 ; Lipid Peroxidation ; Lysosomes; Dependent Anion Channel; Autophagic Cell-death; Histone H3; Lipid-peroxidation; Oxidative Stress; Lysosomes; Aif; Degradation; Glutathione; Proteasome
Sprache englisch
Veröffentlichungsjahr 2021
Prepublished im Jahr 2020
HGF-Berichtsjahr 2020
ISSN (print) / ISBN 0167-4889
e-ISSN 1879-2596
Zeitschrift Biochimica et Biophysica Acta - Molecular Cell Research
Quellenangaben Band: 1868, Heft: 3, Seiten: , Artikelnummer: 118928 Supplement: ,
Verlag Elsevier
Verlagsort Radarweg 29, 1043 Nx Amsterdam, Netherlands
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Metabolism and Cell Death (MCD)
POF Topic(s) 30203 - Molecular Targets and Therapies
Forschungsfeld(er) Genetics and Epidemiology
PSP-Element(e) G-506900-001
Förderungen Wings for Life foundation, Austria
Will-to-Win foundation
DOI 10.1016/j.bbamcr.2020.118928
WOS ID WOS:000608683900009
Scopus ID 85098081475
PubMed ID 33340545
Erfassungsdatum 2021-02-03
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