Podocyte Injury in Diabetic Kidney Disease: A Focus on Mitochondrial Dysfunction

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.

Automated summary

Podocytes are essential for maintaining the glomerular filtration barrier and their injury plays a critical role in the development of albuminuria and diabetic kidney disease (DKD). Mitochondrial dysfunction is a key driver in podocyte injury in DKD, leading to energy crisis, oxidative stress, inflammation, and cell death. This review summarizes the recent advances in understanding the molecular mechanisms of mitochondrial damage and its impact on podocytes. It discusses various mitochondrial pathways involved in podocyte injury in DKD, such as mitochondrial dynamics, mitophagy, mitochondrial biogenesis, oxidative stress, and protein quality control. The review also explores the formation of mitochondria-associated membranes (MAMs) and their role in podocyte mitochondrial function. Finally, it examines the experimental evidence and potential future directions for targeting podocyte mitochondrial function in the treatment of DKD.