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Kabiri, Y.* ; Fuhrmann, A. ; Becker, A. ; Jedermann, L. ; Eberhagen, C. ; König, A. ; Silva, T.B.* ; Borges, F.* ; Hauck, S.M. ; Michalke, B. ; Knolle, P.* ; Zischka, H.

Mitochondrial impairment by MitobloCK-6 inhibits liver cancer cell proliferation. 

Front. Cell Dev. Biol. 9:725474 (2021)
Publ. Version/Full Text Research data DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
Augmenter of liver regeneration (ALR) is a critical multi-isoform protein with its longer isoform, located in the mitochondrial intermembrane space, being part of the mitochondrial disulfide relay system (DRS). Upregulation of ALR was observed in multiple forms of cancer, among them hepatocellular carcinoma (HCC). To shed light into ALR function in HCC, we used MitoBloCK-6 to pharmacologically inhibit ALR, resulting in profound mitochondrial impairment and cancer cell proliferation deficits. These effects were mostly reversed by supplementation with bioavailable hemin b, linking ALR function to mitochondrial iron homeostasis. Since many tumor cells are known for their increased iron demand and since increased iron levels in cancer are associated with poor clinical outcome, these results help to further advance the intricate relation between iron and mitochondrial homeostasis in liver cancer.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Mitochondria ; Hcc ; Disulfide Relay System ; Iron ; Heme; Sulfhydryl Oxidase; Intermembrane Space; Protein; Expression; Iron; Regeneration; Metabolism; Maturation; Sorafenib; Induction
ISSN (print) / ISBN 2296-634X
e-ISSN 2296-634X
Journal Frontiers in cell and developmental biology
Quellenangaben Volume: 9, Issue: , Pages: , Article Number: 725474 Supplement: ,
Publisher Frontiers
Publishing Place Lausanne
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Molecular Toxicology and Pharmacology (TOXI)
Institute of Health Economics and Health Care Management (IGM)
CF Metabolomics & Proteomics (CF-MPC)
Research Unit Analytical BioGeoChemistry (BGC)
Grants FEDER/COMPETE
Foundation for Science and Technology (FCT)
European Unions Horizon 2020 Research and Innovation programme under the Marie Sklodowska-Curie Grant