Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
8287084 | Redox Biology | 2017 | 9 Pages |
Abstract
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
ΔΨmGRP78AMPKMfn1Fis1Mdivi-1TXNIPDrp1BNIP3MFN2ATF6LC3UCP-1PINK1spliced X-box binding protein 1MiD51NF-κBmitochondrial division inhibitor-1TGF-β1sXBP1BCL2/adenovirus E1B 19 kDa interacting protein 3fission protein 1TRX2OMMmTORMFFAMP-activated protein kinaseC/EBP homologous proteinMitochondrial DNAopa1p38 MAPKp62/SQSTM1ROSoptic atrophy 1immTransforming growth factor-β1Thioredoxin 2Oxidative stressCHOPUncoupling protein-1inner mitochondrial membraneType 2 diabetesMitochondrial dynamicsmtDNAredox biologySODSuperoxide dismutaseouter mitochondrial membranemitochondrial fission factornuclear factor kappa Bactivating transcription factor 6mitofusin 1mitofusin 2mammalian target of rapamycin78 kDa glucose-regulated proteinThioredoxin interacting proteindynamin-related protein 1p38 mitogen-activated protein kinaseReactive oxygen species
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Authors
Susana Rovira-Llopis, Celia Bañuls, Noelia Diaz-Morales, Antonio Hernandez-Mijares, Milagros Rocha, Victor M. Victor,