线粒体动力学在糖尿病肾病中的作用及调节机制

doi:10.3760/cma.j.cn441417-20240722-02002

国际医药卫生导报 ›› 2025, Vol. 31 ›› Issue (2): 183-187.DOI: 10.3760/cma.j.cn441417-20240722-02002

线粒体动力学在糖尿病肾病中的作用及调节机制

邢文华梁栋刘洁李梦洁张晓敏

滨州医学院附属医院肾内科，滨州 256603

收稿日期:2024-07-22 出版日期:2025-01-15 发布日期:2025-01-14
通讯作者: 张晓敏，Email：zhangxiaomin7926@126.com
基金资助:
山东省中医药科技项目（Q-2023068）；山东省医药卫生科技发展计划（2017WS689）；滨州医学院科技计划（BY2021KJ07）

Role and regulatory mechanism of mitochondrial dynamics in diabetic nephropathy

Xing Wenhua, Liang Dong, Liu Jie, Li Mengjie, Zhang Xiaomin

Department of Nephrology, Binzhou Medical University Hospital, Binzhou 256600, China

Received:2024-07-22 Online:2025-01-15 Published:2025-01-14
Contact: Zhang Xiaomin, Email: zhangxiaomin7926@126.com
Supported by:
Plan of Science and Technology of Traditional Chinese Medicine in Shandong Province (Q-2023068); Plan for Development of Medicine and Health Science and Technology in Shandong Province (2017WS689); Plan of Science and Technology of Binzhou Medical University (BY2021KJ07)

摘要/Abstract

摘要：

糖尿病肾病（diabetic nephropathy，DN）是一种进展性糖尿病微血管并发症，是糖尿病患者肾衰竭和死亡的主要原因。线粒体裂变与融合过程的平衡对维持线粒体健康和细胞稳态很重要。在DN中，线粒体裂变与融合的不平衡导致的线粒体动力学失衡是核心病理过程。本文就线粒体动力学在DN中的作用、调节机制及针对线粒体动力学的相关靶向药物进行综述，为未来DN的临床治疗提供思路。

关键词:

糖尿病肾病, 线粒体动力学, 线粒体裂变, 线粒体融合, 进展

Abstract:

Diabetic nephropathy (DN) is a progressive microvascular complication of diabetes. It is the main cause of kidney failure and death in diabetic patients. The balance between mitochondrial division and fusion is essential for maintaining cell homeostasis and mitochondrial health. In DN, the imbalance of mitochondrial dynamics caused by the imbalance of mitochondrial fission and fusion is the core pathological process. In this paper, we review the role and regulatory mechanism of mitochondrial dynamics in DN and the relevant targeted drugs targeting mitochondrial dynamics, so as to provide ideas for the future clinical treatment of DN.

Key words:

Diabetic nephropathy, Mitochondrial dynamics, Mitochondrial fission, Mitochondrial fusion, Progress

邢文华梁栋刘洁李梦洁张晓敏.

线粒体动力学在糖尿病肾病中的作用及调节机制 [J]. 国际医药卫生导报, 2025, 31(2): 183-187.

Xing Wenhua, Liang Dong, Liu Jie, Li Mengjie, Zhang Xiaomin.

Role and regulatory mechanism of mitochondrial dynamics in diabetic nephropathy [J]. International Medicine and Health Guidance News, 2025, 31(2): 183-187.

参考文献

[1] Hung PH, Hsu YC, Chen TH, et al. Recent advances in diabetic kidney diseases: from kidney injury to kidney fibrosis [J]. Int J Mol Sci, 2021, 22(21): 11857. DOI: 10.3390/ijms222111857.
[2] Lin YC, Chang YH, Yang SY, et al. Update of pathophysiology and management of diabetic kidney disease [J]. J Formos Med Assoc, 2018, 117(8): 662-675. DOI: 10.1016/j.jfma.2018.02.007.
[3] Barutta F, Bellini S, Gruden G. Mechanisms of podocyte injury and implications for diabetic nephropathy [J]. Clin Sci (Lond), 2022, 136(7): 493-520. DOI: 10.1042/CS20210625.
[4] Maiti AK. Development of biomarkers and molecular therapy based on inflammatory genes in diabetic nephropathy [J]. Int J Mol Sci, 2021, 22(18): 9985. DOI: 10.3390/ijms22189985.
[5] Mishra P, Chan DC. Metabolic regulation of mitochondrial dynamics [J]. J Cell Biol, 2016, 212(4): 379-387. DOI: 10.1083/jcb.201511036.
[6] Jiang Y, Krantz S, Qin X, et al. Caveolin-1 controls mitochondrial damage and ROS production by regulating fission - fusion dynamics and mitophagy [J]. Redox Biol, 2022, 52: 102304. DOI: 10.1016/j.redox.2022.102304.
[7] Whitley BN, Engelhart EA, Hoppins S. Mitochondrial dynamics and their potential as a therapeutic target [J]. Mitochondrion, 2019, 49: 269-283. DOI: 10.1016/j.mito.2019.06.002.
[8] Kleele T, Rey T, Winter J, et al. Distinct fission signatures predict mitochondrial degradation or biogenesis [J]. Nature, 2021, 593(7859): 435-439. DOI: 10.1038/s41586-021-03510-6.
[9] Chang X, Li Y, Cai C, et al. Mitochondrial quality control mechanisms as molecular targets in diabetic heart [J]. Metabolism, 2022, 137: 155313. DOI: 10.1016/j.metabol.2022.155313.
[10] Sun Q, Jia H, Cheng S, et al. Metformin alleviates epirubicin-induced endothelial impairment by restoring mitochondrial homeostasis [J]. Int J Mol Sci, 2022, 24(1): 343. DOI: 10.3390/ijms24010343.
[11] Sabouny R, Shutt TE. Reciprocal regulation of mitochondrial fission and fusion [J]. Trends Biochem Sci, 2020, 45(7): 564-577. DOI: 10.1016/j.tibs.2020.03.009.
[12] Gao P, Yang M, Chen X, et al. DsbA-L deficiency exacerbates mitochondrial dysfunction of tubular cells in diabetic kidney disease [J]. Clin Sci (Lond), 2020, 134(7): 677-694. DOI: 10.1042/CS20200005.
[13] Sheng J, Li H, Dai Q, et al. DUSP1 recuses diabetic nephropathy via repressing JNK-Mff-mitochondrial fission pathways [J]. J Cell Physiol, 2019, 234(3): 3043-3057. DOI: 10.1002/jcp.27124.
[14] Liu S, Yuan Y, Xue Y, et al. Podocyte injury in diabetic kidney disease: a focus on mitochondrial dysfunction [J]. Front Cell Dev Biol, 2022, 10: 832887. DOI: 10.3389/fcell.2022.832887.
[15] Liu S, Li X, Wen R, et al. Increased thromboxane/prostaglandin receptors contribute to high glucose-induced podocyte injury and mitochondrial fission through ROCK1-Drp1 signaling [J]. Int J Biochem Cell Biol, 2022, 151: 106281. DOI: 10.1016/j.biocel. 2022.106281.
[16] Hongbo M, Yanjiao D, Shuo W, et al. Podocyte RNF166 deficiency alleviates diabetic nephropathy by mitigating mitochondria impairment and apoptosis via regulation of CYLD signal [J]. Biochem Biophys Res Commun, 2021, 545: 46-53. DOI: 10.1016/j.bbrc.2020.12.014.
[17] Chen Z, Ma Y, Yang Q, et al. AKAP1 mediates high glucose-induced mitochondrial fission through the phosphorylation of Drp1 in podocytes [J]. J Cell Physiol, 2020, 235(10): 7433-7448. DOI: 10.1002/jcp.29646.
[18] Wang S, Yang Y, He X, et al. Cdk5-mediated phosphorylation of Sirt1 contributes to podocyte mitochondrial dysfunction in diabetic nephropathy [J]. Antioxid Redox Signal, 2021, 34(3): 171-190. DOI: 10.1089/ars.2020.8038.
[19] Wu QR, Zheng DL, Liu PM, et al. High glucose induces Drp1-mediated mitochondrial fission via the Orai1 calcium channel to participate in diabetic cardiomyocyte hypertrophy [J]. Cell Death Dis, 2021, 12(2): 216. DOI: 10.1038/s41419-021-03502-4.
[20] Zhan M, Usman I, Yu J, et al. Perturbations in mitochondrial dynamics by p66Shc lead to renal tubular oxidative injury in human diabetic nephropathy [J]. Clin Sci (Lond), 2018, 132(12): 1297-1314. DOI: 10.1042/CS20180005.
[21] Ayanga BA, Badal SS, Wang Y, et al. Dynamin-related protein 1 deficiency improves mitochondrial fitness and protects against progression of diabetic nephropathy [J]. J Am Soc Nephrol, 2016, 27(9): 2733-2747. DOI: 10.1681/ASN.2015101096.
[22] Cleveland KH, Brosius FC, Schnellmann RG. Regulation of mitochondrial dynamics and energetics in the diabetic renal proximal tubule by the β2-adrenergic receptor agonist formoterol [J]. Am J Physiol Renal Physiol, 2020, 319(5): F773-F779. DOI: 10.1152/ajprenal.00427.2020.
[23] Shen L, Zhang Q, Tu S, et al. SIRT3 mediates mitofusin 2 ubiquitination and degradation to suppress ischemia reperfusion-induced acute kidney injury [J]. Exp Cell Res, 2021, 408(2): 112861. DOI: 10.1016/j.yexcr.2021.112861.
[24] Ren G, Guo JH, Feng CL, et al. Berberine inhibits carcinogenesis through antagonizing the ATX-LPA-LPAR2-p38-leptin axis in a mouse hepatoma model [J]. Mol Ther Oncolytics, 2022, 26: 372-386. DOI: 10.1016/j.omto.2022.08.001.
[25] Zhao MM, Lu J, Li S, et al. Author Correction: berberine is an insulin secretagogue targeting the KCNH6 potassium channel [J]. Nat Commun, 2021, 12(1): 6342. DOI: 10.1038/s41467-021-26635-8.
[26] Hu S, Wang J, Liu E, et al. Protective effect of berberine in diabetic nephropathy: a systematic review and meta-analysis revealing the mechanism of action [J]. Pharmacol Res, 2022, 185: 106481. DOI: 10.1016/j.phrs.2022.106481.
[27] Qin X, Zhao Y, Gong J, et al. Berberine protects glomerular podocytes via Inhibiting Drp1-mediated mitochondrial fission and dysfunction [J]. Theranostics, 2019, 9(6): 1698-1713. DOI: 10.7150/thno.30640.
[28] Lee YH, Kim SH, Kang JM, et al. Empagliflozin attenuates diabetic tubulopathy by improving mitochondrial fragmentation and autophagy [J]. Am J Physiol Renal Physiol, 2019, 317(4): F767-F780. DOI: 10.1152/ajprenal.00565.2018.
[29] Ni Z, Tao L, Xiaohui X, et al. Polydatin impairs mitochondria fitness and ameliorates podocyte injury by suppressing Drp1 expression [J]. J Cell Physiol, 2017, 232(10): 2776-2787. DOI: 10.1002/jcp.25943.
[30] Agil A, Chayah M, Visiedo L, et al. Melatonin improves mitochondrial dynamics and function in the kidney of Zücker diabetic fatty rats [J]. J Clin Med, 2020, 9(9): 2916. DOI: 10.3390/jcm9092916.

线粒体动力学在糖尿病肾病中的作用及调节机制

Role and regulatory mechanism of mitochondrial dynamics in diabetic nephropathy

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