Abstract
Podocytes are a crucial cellular component in maintaining the glomerular filtration barrier, and their injury is the major determinant in the development of albuminuria and diabetic kidney disease (DKD). Podocytes are rich in mitochondria and heavily dependent on them for energy to maintain normal functions. Emerging evidence suggests that mitochondrial dysfunction is a key driver in the pathogenesis of podocyte injury in DKD. Impairment of mitochondrial function results in an energy crisis, oxidative stress, inflammation, and cell death. In this review, we summarize the recent advances in the molecular mechanisms that cause mitochondrial damage and illustrate the impact of mitochondrial injury on podocytes. The related mitochondrial pathways involved in podocyte injury in DKD include mitochondrial dynamics and mitophagy, mitochondrial biogenesis, mitochondrial oxidative phosphorylation and oxidative stress, and mitochondrial protein quality control. Furthermore, we discuss the role of mitochondria-associated membranes (MAMs) formation, which is intimately linked with mitochondrial function in podocytes. Finally, we examine the experimental evidence exploring the targeting of podocyte mitochondrial function for treating DKD and conclude with a discussion of potential directions for future research in the field of mitochondrial dysfunction in podocytes in DKD.
Highlights
Diabetic kidney disease (DKD) is the leading cause of end-stage renal disease (ESRD), and it affects nearly 30–40% of patients with diabetes (Alicic et al, 2017)
The regulation of podocyte mitochondrial dysfunction in patients with diabetic kidney disease (DKD) has been extensively studied in the past few years, but few reviews have thoroughly summarized the progress in this area
A comprehensive investigation of mitochondrial damage and its potential regulatory mechanisms could provide a deeper understanding of podocyte injury and possible therapeutic options that could have a positive impact on the treatment of DKD
Summary
Diabetic kidney disease (DKD) is the leading cause of end-stage renal disease (ESRD), and it affects nearly 30–40% of patients with diabetes (Alicic et al, 2017). The principal feature of DKD is an abnormality of the glomerular filtration barrier (GFB), leading to the leakage of protein (proteinuria), metabolites and ions into the urine. Proteinuria simultaneously acts as a major, independent risk factor for the progression of DKD to ESRD. Podocytes form the outer part and ensure the mechanical stability of the GFB, preventing protein loss into the urine. Podocyte dysfunction is one of the earliest glomerular morphologic changes and it plays a key role in DKD progression (Wang et al, 2012; Reidy et al, 2014; Qi et al, 2017). Hyperglycemia is the most predominant clinical abnormality in diabetes, and it has been viewed as one of the leading risk
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