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Int J Biol Sci 2023; 19(14):4427-4441. doi:10.7150/ijbs.86608 This issue Cite

Review

Broadening horizons: the contribution of mitochondria-associated endoplasmic reticulum membrane (MAM) dysfunction in diabetic kidney disease

Yong Liu^1,2,3,4, Yingjin Qiao⁵, Shaokang Pan^1,2,3,4, Jingfang Chen^1,2,3,4, Zihui Mao^1,2,3,4, Kaidi Ren⁶, Yang Yang⁷, Qi Feng^1,2,3,4✉, Dongwei Liu^1,2,3,4✉, Zhangsuo Liu^1,2,3,4✉

1. Research Institute of Nephrology, Zhengzhou University, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, P. R. China.
2. Traditional Chinese Medicine Integrated Department of Nephrology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, P. R. China.
3. Henan Province Research Center for Kidney Disease, Zhengzhou 450052, P. R. China.
4. Key Laboratory of Precision Diagnosis and Treatment for Chronic Kidney Disease in Henan Province, Zhengzhou 450052, P. R. China
5. Blood Purification Center, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, P. R. China.
6. Department of Pharmacy, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, P. R. China.
7. Clinical Systems Biology Laboratories, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, P. R. China.

✉ Corresponding authors: Qi Feng, Dongwei Liu and Zhangsuo Liu, Research Institute of Nephrology, Zhengzhou University, Traditional Chinese Medicine Integrated Department of Nephrology, Henan Province Research Center for Kidney Disease, Key Laboratory of Precision Diagnosis and Treatment for Chronic Kidney Disease in Henan Province, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China. Email: fengqi2019edu.cn; liu-dongweiedu.cn; zhangsuoliuedu.cn. More

Abstract

Diabetic kidney disease (DKD) is a global health issue that presents a complex pathogenesis and limited treatment options. To provide guidance for precise therapies, it is crucial to accurately identify the pathogenesis of DKD. Several studies have recognized that mitochondrial and endoplasmic reticulum (ER) dysfunction are key drivers of the pathogenesis of DKD. The mitochondria-associated ER membrane (MAM) is a dynamic membrane contact site (MSC) that connects the ER and mitochondria and is essential in maintaining the normal function of the two organelles. MAM is involved in various cellular processes, including lipid synthesis and transport, calcium homeostasis, mitochondrial fusion and fission, and ER stress. Meanwhile, recent studies confirm that MAM plays a significant role in the pathogenesis of DKD by regulating glucose metabolism, lipid metabolism, inflammation, ER stress, mitochondrial fission and fusion, and autophagy. Herein, this review aims to provide a comprehensive summary of the physiological function of MAMs and their impact on the progression of DKD. Subsequently, we discuss the trend of pharmaceutical studies that target MAM resident proteins for treating DKD. Furthermore, we also explore the future development prospects of MAM in DKD research, thereby providing a new perspective for basic studies and clinical treatment of DKD.

Keywords: Mitochondria-associated endoplasmic reticulum membrane (MAM), diabetic kidney disease (DKD), mitochondrial physiology, calcium homeostasis, lipid metabolism

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