Role of mitophagy in mitochondrial quality control: Mechanisms and potential implications for neurodegenerative diseases

Pharmacol Res. 2021 Mar:165:105433. doi: 10.1016/j.phrs.2021.105433. Epub 2021 Jan 14.

Abstract

Neurodegenerative diseases (e.g., Alzheimer's disease, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis) commonly characterized by the gradual loss of neurons have a seriously bad impact on motor and cognitive abilities of affected humans and bring great inconvenience to their lives. Mitochondrial dysfunction has been considered the key and common factor for the pathologies of neurodegenerative diseases for that neurons are extremely energy-intensive due to their unique properties in structures and functions. Thus, mitophagy, as a central role of mitochondrial quality control and currently believed to be the most effective pathway to clear dysfunctional or unwanted mitochondria, is rather crucial in the preservation of neuronal health. In addition, mitophagy establishes an intimated link with several other pathways of mitochondrial quality control (e.g., mitochondrial biogenesis and mitochondrial dynamics), and they work together to preserve mitochondrial health. Therefore, in this review, we summarized the recent process on the mechanisms of mitophagy pathways in mammals, it's linking to mitochondrial quality control, its role in several major neurodegenerative diseases, and possible therapeutic interventions focusing on mitophagy pathways. And we expect that it can provide us with more understanding of the mitophagy pathways and more promising approaches for the treatment of neurodegenerative diseases.

Keywords: Alzheimer’s disease; Amyotrophic lateral sclerosis; Huntington’s disease; Mitochondrial quality control; Mitophagy; Parkinson’s disease.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Autophagy / physiology
  • Humans
  • Mitochondria / metabolism*
  • Mitochondria / pathology
  • Mitochondrial Dynamics / physiology*
  • Mitophagy / physiology*
  • Neurodegenerative Diseases / metabolism*
  • Neurodegenerative Diseases / pathology
  • Signal Transduction / physiology