The Mitochondria-Targeted Metabolic Tubular Injury in Diabetic Kidney Disease

Cellular Physiology and Biochemistry : International Journal of Experimental Cellular Physiology, Biochemistry, and Pharmacology
Hong JiangJianghua Chen

Abstract

Diabetic kidney disease (DKD) is a leading cause of end-stage renal disease (ESRD) worldwide, and the importance of tubular injury has been highlighted in recent years. However, the underlying mechanisms and effective therapeutic targets are still unclear. In this study, we investigated mtDNA, mitochondrial dynamics, function and metabolic pathways to determine if mitochondrial damage plays a critical role in the development of tubular injury in DKD patients. A cross-sectional study was carried out among healthy controls (HCs, n = 65), diabetes patients without kidney disease (DCs, n = 48) and DKD patients (n = 60). Serum, peripheral blood mononuclear cells (PBMCs) and kidney biopsy specimens were obtained from participants. Metabolomics was employed to investigate cellular metabolism. DKD patients had decreased mtDNA copy numbers and increased mtDNA damage compared to DCs. Mitochondrial fragmentation was specifically presented in tubules, but not in podocytes of DKD patients. The accumulation of damaged mtDNA and fragmented mitochondria resulted in increased reactive oxygen species (ROS) generation, activation of apoptosis and loss of mitochondrial membrane potential (ΔΨm) in tubules and PBMCs. Furthermore, glycolysis and tric...Continue Reading

Citations

Jul 16, 2020·BMC Nephrology·Huanhuan ZhuYanggang Yuan
Dec 6, 2019·Frontiers in Molecular Biosciences·Dayan SunJiucun Wang
Dec 15, 2019·International Journal of Molecular Sciences·Afshan N MalikSobha Sivaprasad
Sep 22, 2020·American Journal of Physiology. Renal Physiology·Kristan H ClevelandRick G Schnellmann
Aug 1, 2020·International Journal of Endocrinology·Yajing HuangYangang Wang
Jan 16, 2021·Current Diabetes Reports·Robert C Stanton
Jan 12, 2021·Frontiers in Endocrinology·Jingyu WangBaocheng Chang
Jun 18, 2021·Mechanisms of Ageing and Development·Benjamin DilbergerGunter P Eckert
Jul 1, 2021·Kidney360·Koki MiseFarhad R Danesh
Aug 24, 2021·Frontiers in Cell and Developmental Biology·Wenni DaiLiyu He
Sep 23, 2021·Therapeutic Apheresis and Dialysis : Official Peer-reviewed Journal of the International Society for Apheresis, the Japanese Society for Apheresis, the Japanese Society for Dialysis Therapy·Jun-Jie ZhuPing Zhou

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