The Role of Mitochondrial Quality Control in Cognitive Dysfunction in Diabetes

Neurochem Res. 2022 Aug;47(8):2158-2172. doi: 10.1007/s11064-022-03631-y. Epub 2022 Jun 4.

Abstract

Type 2 diabetes (T2DM) is a well known risk factor for Alzheimer's disease. Mitochondria are the center of intracellular energy metabolism and the main source of reactive oxygen species. Mitochondrial dysfunction has been identified as a key factor in diabetes-associated brain alterations contributing to neurodegenerative events. Defective insulin signaling may act in concert with neurodegenerative mechanisms leading to abnormalities in mitochondrial structure and function. Mitochondrial dysfunction triggers neuronal energy exhaustion and oxidative stress, leading to brain neuronal damage and cognitive impairment. The normality of mitochondrial function is basically maintained by mitochondrial quality control mechanisms. In T2DM, defects in the mitochondrial quality control pathway in the brain have been found to lead to mitochondrial dysfunction and cognitive impairment. Here, we discuss the association of mitochondrial dysfunction with T2DM and cognitive impairment. We also review the molecular mechanisms of mitochondrial quality control and impacts of mitochondrial quality control on the progression of cognitive impairment in T2DM.

Keywords: Cognitive dysfunction; Diabetes; Mitochondria; Mitochondrial quality control.

Publication types

  • Review

MeSH terms

  • Alzheimer Disease* / metabolism
  • Cognitive Dysfunction* / metabolism
  • Diabetes Mellitus, Type 2* / complications
  • Diabetes Mellitus, Type 2* / metabolism
  • Humans
  • Mitochondria / metabolism
  • Oxidative Stress / physiology
  • Reactive Oxygen Species / metabolism

Substances

  • Reactive Oxygen Species