Mitochondrial damage and cholesterol storage in human hepatocellular carcinoma cells with silencing of UBIAD1 gene expression

Carlos R Morales; Lubov S Grigoryeva; Xuefang Pan; Luigi Bruno; Gilles Hickson; Michael H Ngo; Christopher R McMaster; Mark E Samuels; Alexey V Pshezhetsky

doi:10.1016/j.ymgmr.2014.09.001

Mitochondrial damage and cholesterol storage in human hepatocellular carcinoma cells with silencing of UBIAD1 gene expression

Mol Genet Metab Rep. 2014 Sep 19:1:407-411. doi: 10.1016/j.ymgmr.2014.09.001. eCollection 2014.

Authors

Carlos R Morales¹, Lubov S Grigoryeva², Xuefang Pan², Luigi Bruno², Gilles Hickson³, Michael H Ngo⁴, Christopher R McMaster⁴, Mark E Samuels⁵, Alexey V Pshezhetsky⁶

Affiliations

¹ Department of Anatomy and Cell Biology, Faculty of Medicine, McGill University, Montreal, Quebec, Canada.
² CHU Sainte-Justine Research Center, Montreal, Quebec, Canada.
³ CHU Sainte-Justine Research Center, Montreal, Quebec, Canada; Department of Pathology and Cell Biology, University of Montreal, Montreal, Quebec, Canada.
⁴ Department of Pharmacology, Dalhousie University, Halifax, Nova Scotia, Canada.
⁵ CHU Sainte-Justine Research Center, Montreal, Quebec, Canada; Department of Medicine, University of Montreal, Montreal, Quebec, Canada.
⁶ Department of Anatomy and Cell Biology, Faculty of Medicine, McGill University, Montreal, Quebec, Canada; CHU Sainte-Justine Research Center, Montreal, Quebec, Canada; Departments of Paediatrics and Biochemistry, University of Montreal, Montreal, Quebec, Canada.

Abstract

Heterozygous mutations in the UBIAD1 gene cause Schnyder corneal dystrophy characterized by abnormal cholesterol and phospholipid deposits in the cornea. Ubiad1 protein was recently identified as Golgi prenyltransferase responsible for biosynthesis of vitamin K2 and CoQ10, a key protein in the mitochondrial electron transport chain. Our study shows that silencing UBIAD1 in cultured human hepatocellular carcinoma cells causes dramatic morphological changes and cholesterol storage in the mitochondria, emphasizing an important role of UBIAD1 in mitochondrial function.

Keywords: Cholesterol; CoQ10; Mitochondrion; Reactive oxygen species; Schnyder corneal dystrophy.