The Loss of Mitochondrial Quality Control in Diabetic Kidney Disease.

Wenni Dai,Hengcheng Lu,Lin Sun,Liyu He,Yinyin Chen,Danyi Yang

doi:10.3389/fcell.2021.706832

Abstract

Diabetic kidney disease (DKD) is the predominant complication of diabetes mellitus (DM) and the leading cause of chronic kidney disease and end-stage renal disease worldwide, which are major risk factors for death. The pathogenesis of DKD is very complicated, including inflammation, autophagy impairment, oxidative stress, and so on. Recently, accumulating evidence suggests that the loss of mitochondrial quality control exerts critical roles in the progression of DKD. Mitochondria are essential for eukaryotic cell viability but are extremely vulnerable to damage. The mechanisms of mitochondrial quality control act at the molecular level and the organelle level, including mitochondrial dynamics (fusion and fission), mitophagy, mitochondrial biogenesis, and mitochondrial protein quality control. In this review, we summarize current knowledge of the role of disturbances in mitochondrial quality control in the pathogenesis of DKD and provide potential insights to explore how to delay the onset and development of DKD.

Highlights

Mitochondria are one of the important intracellular organelles that participate in a broad array of functions in mammals (Dimmer and Scorrano, 2006)
Hyperglycemia induced the down-regulation of PGC-1α, which leads to mitochondrial biogenesis disorder, resulting in increased DRP1 expression, increased mitochondrial fragmentation, and impaired mitochondrial network structure
The role of PGC-1α is essential in controlling the process of mitochondrial biogenesis (Scarpulla, 2011), pharmacological activation of PGC1α serves as a novel and potential approach to improve this disease of Diabetic kidney disease (DKD)

Summary

Introduction

Mitochondria are one of the important intracellular organelles that participate in a broad array of functions in mammals (Dimmer and Scorrano, 2006). Mitochondrial fission and fusion events separate damaged mitochondria, meet the energy demands of cells and provide a mitochondrial quality control mechanism (Forbes and Thorburn, 2018). Mitophagy acts as a critical component of mitochondrial quality control mechanism that mediates clearance of damaged and unwanted mitochondria, renew components (Ashrafi and Schwarz, 2013; Pickles et al, 2018).

Results

Conclusion