Mitochondrial dynamics in type 2 diabetes: Pathophysiological implications

被引:450
作者
Rovira-Llopis, Susana [1 ]
Banuls, Celia [1 ]
Diaz-Morales, Noelia [1 ]
Hernandez-Mijares, Antonio [1 ,2 ]
Rocha, Milagros [1 ,3 ]
Victor, Victor M. [1 ,3 ,4 ]
机构
[1] Univ Hosp Doctor Peset, Fdn Promot Hlth & Biomed Res Valencian Reg FISABI, Serv Endocrinol & Nutr, Valencia, Spain
[2] Univ Valencia, Dept Med, Valencia, Spain
[3] Univ Valencia, CIBERehd Dept Pharmacol, Valencia, Spain
[4] Univ Valencia, Dept Physiol, Valencia, Spain
来源
REDOX BIOLOGY | 2017年 / 11卷
关键词
Mitochondrial dynamics; Type; 2; diabetes; Redox biology; Oxidative stress; HUMAN SKELETAL-MUSCLE; BETA-CELL FUNCTION; INSULIN-RESISTANCE; CONTRACTILE DYSFUNCTION; OXIDATIVE STRESS; GLUCOSE CONTROL; QUALITY-CONTROL; ADIPOSE-TISSUE; FISSION; MITOPHAGY;
D O I
10.1016/j.redox.2017.01.013
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Mitochondria play a key role in maintaining cellular metabolic homeostasis. These organelles have a high plasticity and are involved in dynamic processes such as mitochondrial fusion and fission, mitophagy and mitochondrial biogenesis. Type 2 diabetes is characterised by mitochondrial dysfunction, high production of reactive oxygen species (ROS) and low levels of ATP. Mitochondrial fusion is modulated by different proteins, including mitofusin-1 (MFN1), mitofusin-2 (MFN2) and optic atrophy (OPA-1), while fission is controlled by mitochondrial fission 1 (FIS1), dynamin-related protein 1 (DRP1) and mitochondrial fission factor (MFF). PARKIN and (PTEN)-induced putative kinase 1 (PINK1) participate in the process of mitophagy, for which mitochondrial fission is necessary. In this review, we discuss the molecular pathways of mitochondrial dynamics, their impairment under type 2 diabetes, and pharmaceutical approaches for targeting mitochondrial dynamics, such as mitochondrial division inhibitor-1 (mdivi-1), dynasore, P110 and 15-oxospiramilactone. Furthermore, we discuss the pathophysiological implications of impaired mitochondrial dynamics, especially in type 2 diabetes.
引用
收藏
页码:637 / 645
页数:9
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