Identification and clinical implication of biomarkers for mitochondrial diseases

2019 Fiscal Year Annual Research Report

• Project/Area Number: 18K15698
• Research Institution: Hokkaido University
• Principal Investigator: 何 欣蓉 北海道大学, 保健科学研究院, 特任講師 (50815561)
• Project Period (FY): 2018-04-01 – 2020-03-31
• Keywords: mitochondria / kidney / lipid / cardiolipin

Outline of Annual Research Achievements

The accumulated lipids might induce mitochondrial dysfunction in the renal proximal tubule cell, however, the differences between saturated and unsaturated fatty acid for lipid droplets formation and accumulation are still unknown. Mitochondrial dysfunction results in decreasing ATP production, altering cellular functions and impaired renal function. Improving mitochondrial function may provide a novel therapeutic approach to minimize renal injury and slow chronic kidney disease (CKD) progression.
In current study, lipid droplets accumulated in both saturated and unsaturated fatty acids in human proximal tubular HK-2 cells, however, lipotoxicity accompanied by increased double bonds of unsaturated fatty acids but not saturated fatty acid (palmitic acid, 16:0) in HK-2 cells using cytotoxicity assay. Further, the production of ATP decreased in unsaturated fatty acid (oleic acid, 18:1) treated cells at 3 hours, suggesting that the function of mitochondria might decreased. Cardiolipin (CL) is a phospholipid localized in the mitochondrial membrane that CL plays a critical role in mitochondrial function. CL composition changed with the composition of saturated fatty acid (palmitic acid, 16:0) and unsaturated fatty acid (oleic acid, 18:1), the investigation of CL composition could be a potential tool to understanding the progression of CKD.