New therapeutic directions in type II diabetes and its complications: mitochondrial dynamics

Frontiers in Endocrinology

Endocrinology

Shengnan Wang¹  Yang Lv¹  Suxian Lin¹  Huanzhi Jin²  Yue Lin²  Renyi Peng³  Yinai Liu³  Haiyang Zhao³ 

[1] Department of Rheumatology and Immunology, The Third Affiliated Hospital of Shanghai University, Wenzhou No.3 Clinical Institute Affiliated to Wenzhou Medical University, Wenzhou People’s Hospital, Wenzhou, China;General Practitioner, The Third Affiliated Hospital of Shanghai University, Wenzhou No.3 Clinical Institute Affiliated to Wenzhou Medical University, Wenzhou People’s Hospital, Wenzhou, China;Institute of Life Sciences & Biomedicine Collaborative Innovation Center of Zhejiang, College of Life and Environmental Science, Wenzhou University, Wenzhou, China;

关键词: mitochondrial dynamics;    mitochondrial fusion;    mitochondrial fission;    type II diabetes;    diabetic complications;   

DOI  :  10.3389/fendo.2023.1230168

 received in 2023-05-28, accepted in 2023-08-07,  发布年份 2023

来源: Frontiers

【 摘 要 】

As important organelles of energetic and metabolism, changes in the dynamic state of mitochondria affect the homeostasis of cellular metabolism. Mitochondrial dynamics include mitochondrial fusion and mitochondrial fission. The former is coordinated by mitofusin-1 (Mfn1), mitofusin-2 (Mfn2), and optic atrophy 1 (Opa1), and the latter is mediated by dynamin related protein 1 (Drp1), mitochondrial fission 1 (Fis1) and mitochondrial fission factor (MFF). Mitochondrial fusion and fission are generally in dynamic balance and this balance is important to preserve the proper mitochondrial morphology, function and distribution. Diabetic conditions lead to disturbances in mitochondrial dynamics, which in return causes a series of abnormalities in metabolism, including decreased bioenergy production, excessive production of reactive oxygen species (ROS), defective mitophagy and apoptosis, which are ultimately closely linked to multiple chronic complications of diabetes. Multiple researches have shown that the incidence of diabetic complications is connected with increased mitochondrial fission, for example, there is an excessive mitochondrial fission and impaired mitochondrial fusion in diabetic cardiomyocytes, and that the development of cardiac dysfunction induced by diabetes can be attenuated by inhibiting mitochondrial fission. Therefore, targeting the restoration of mitochondrial dynamics would be a promising therapeutic target within type II diabetes (T2D) and its complications. The molecular approaches to mitochondrial dynamics, their impairment in the context of T2D and its complications, and pharmacological approaches targeting mitochondrial dynamics are discussed in this review and promise benefits for the therapy of T2D and its comorbidities.

【 授权许可】

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Copyright © 2023 Wang, Zhao, Lin, Lv, Lin, Liu, Peng and Jin