AUTHOR=Kabiri Yaschar , Fuhrmann Anna , Becker Anna , Jedermann Luisa , Eberhagen Carola , König Ann-Christine , Silva Tiago Barros , Borges Fernanda , Hauck Stefanie M. , Michalke Bernhard , Knolle Percy , Zischka Hans TITLE=Mitochondrial Impairment by MitoBloCK-6 Inhibits Liver Cancer Cell Proliferation JOURNAL=Frontiers in Cell and Developmental Biology VOLUME=9 YEAR=2021 URL=https://www.frontiersin.org/journals/cell-and-developmental-biology/articles/10.3389/fcell.2021.725474 DOI=10.3389/fcell.2021.725474 ISSN=2296-634X ABSTRACT=

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.