Mitochondrial dynamics in type 2 diabetes: Pathophysiological implications

Redox Biol. 2017 Apr;11:637-645. doi: 10.1016/j.redox.2017.01.013. Epub 2017 Jan 16.

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: Mitochondrial dynamics; Oxidative stress; Redox biology; Type 2 diabetes.

Publication types

  • Review

MeSH terms

  • Adenosine Triphosphate / metabolism
  • Diabetes Mellitus, Type 2 / genetics
  • Diabetes Mellitus, Type 2 / metabolism*
  • Diabetes Mellitus, Type 2 / physiopathology
  • Humans
  • Mitochondria / genetics
  • Mitochondria / metabolism*
  • Mitochondria / pathology
  • Mitochondrial Dynamics / genetics
  • Mitochondrial Dynamics / physiology
  • Mitochondrial Proteins / genetics
  • Mitochondrial Proteins / metabolism*
  • Mitophagy / genetics*
  • Mitophagy / physiology
  • Reactive Oxygen Species / metabolism

Substances

  • Mitochondrial Proteins
  • Reactive Oxygen Species
  • Adenosine Triphosphate