The role of mitochondrial-associated endoplasmic reticulum membranes (MAMs) in diabetic microvascular complications: a review

Diabetic vascular complications include macrovascular lesions and microvascular lesions. Diabetic microvascular complications (DMC) are mainly manifested by microvascular endothelial dysfunction, basement membrane thickening, capillary permeability changes and microthrombosis, which may contribute to the occurrence of kidney, cardiac, ocular and peripheral system damage in diabetic individuals. Thus, it is urgent to develop new prevention and treatment strategies. The mitochondria-associated endoplasmic reticulum membranes (MAMs), as a highly heterogeneous membrane contact site, play a key role in maintaining biological communication between the endoplasmic reticulum (ER) and mitochondria. Studies have shown that MAMs are involved in the pathogenesis of DMC by regulating Ca²⁺ homeostasis, lipid synthesis and transport, mitochondrial dynamics, ER stress, glucose homeostasis, autophagy, apoptosis, and inflammation. This review comprehensively summarizes the complex structure and key biological functions of MAMs that drive the physiological transmission of substances and signals between organelles. Furthermore, we focused on exploring the regulatory mechanism of MAMs on different diabetic microangiopathies, including diabetic kidney disease (DKD), diabetic cardiomyopathy (DCM), and diabetic retinopathy (DR). In conclusion, targeting MAMs is a promising but challenging therapeutic strategy.