The role of endoplasmic reticulum–mitochondria-associated membranes in diabetic kidney disease

Abstract Diabetic kidney disease (DKD) is the leading cause of end-stage renal disease worldwide. The pathomechanisms of DKD are multifactorial, yet haemodynamic and metabolic changes in the early stages of the disease appear to predispose towards irreversible functional loss and histopathological changes. Recent studies highlight the importance of endoplasmic reticulum–mitochondria-associated membranes (ER-MAMs), structures conveying important cellular homeostatic and metabolic effects, in the pathology of DKD. Disruption of ER-MAM integrity in diabetic kidneys is associated with DKD progression, but the regulation of ER-MAMs and their pathogenic contribution remain largely unknown. Exploring the cell-specific components and dynamic changes of ER-MAMs in diabetic kidneys may lead to the identification of new approaches to detect and stratify diabetic patients with DKD. In addition, these insights may lead to novel therapeutic approaches to target and/or reverse disease progression. In this review, we discuss the association of ER-MAMs with key pathomechanisms driving DKD such as insulin resistance, dyslipidaemia, ER stress, and inflammasome activation and the importance of further exploration of ER-MAMs as diagnostic and therapeutic targets in DKD.