Mitochondrial dynamics in type 2 diabetes: Pathophysiological implications
Susana Rovira-Llopis,
Celia Bañuls,
Noelia Diaz-Morales,
Antonio Hernandez-Mijares,
Milagros Rocha,
Victor M. Victor
Affiliations
Susana Rovira-Llopis
Service of Endocrinology and Nutrition, University Hospital Doctor Peset, Foundation for the Promotion of Health and Biomedical Research in the Valencian Region (FISABIO), Valencia, Spain
Celia Bañuls
Service of Endocrinology and Nutrition, University Hospital Doctor Peset, Foundation for the Promotion of Health and Biomedical Research in the Valencian Region (FISABIO), Valencia, Spain
Noelia Diaz-Morales
Service of Endocrinology and Nutrition, University Hospital Doctor Peset, Foundation for the Promotion of Health and Biomedical Research in the Valencian Region (FISABIO), Valencia, Spain
Antonio Hernandez-Mijares
Service of Endocrinology and Nutrition, University Hospital Doctor Peset, Foundation for the Promotion of Health and Biomedical Research in the Valencian Region (FISABIO), Valencia, Spain; Department of Medicine, University of Valencia, Valencia, Spain
Milagros Rocha
Service of Endocrinology and Nutrition, University Hospital Doctor Peset, Foundation for the Promotion of Health and Biomedical Research in the Valencian Region (FISABIO), Valencia, Spain; CIBERehd - Department of Pharmacology, University of Valencia, Valencia, Spain
Victor M. Victor
Service of Endocrinology and Nutrition, University Hospital Doctor Peset, Foundation for the Promotion of Health and Biomedical Research in the Valencian Region (FISABIO), Valencia, Spain; CIBERehd - Department of Pharmacology, University of Valencia, Valencia, Spain; Department of Physiology, University of Valencia, Valencia, Spain; Correspondence to: FISABIO, University Hospital Doctor Peset, Avda Gaspar Aguilar 90, 46017 Valencia, Spain
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. Keywords: Mitochondrial dynamics, Type 2 diabetes, Redox biology, Oxidative stress
