Mitofusin-2: Functional switch between mitochondrial function and neurodegeneration

Mitochondrion. 2023 Mar:69:116-129. doi: 10.1016/j.mito.2023.02.001. Epub 2023 Feb 9.

Abstract

Mitochondria are highly dynamic organelles known to play role in the regulation of several cellular biological processes. However, their dynamics such as number, shape, and biological functions are regulated by mitochondrial fusion and fission process. The balance between the fusion and fission process is most important for the maintenance of mitochondrial structure as well as cellular functions. The alterations within mitochondrial dynamic processes were found to be associated with the progression of neurodegenerative diseases. In recent years, mitofusin-2 (Mfn2), a GTPase has emerged as a multifunctional protein which not only is found to regulate the mitochondrial fusion-fission process but also known to regulate several cellular functions such as mitochondrial metabolism, cellular biogenesis, signalling, and apoptosis via maintaining the ER-mitochondria contact sites. In this review, we summarize the current knowledge of the structural and functional properties of the Mfn2, its transcriptional regulation and their roles in several cellular functions with a focus on current advances in the pathogenesis of neurodegenerative diseases.

Keywords: Alzheimer’s disease; Mitochondria associated membranes; Mitofusin-2; Neurodegeneration; Parkinson’s disease.

Publication types

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

MeSH terms

  • Apoptosis
  • GTP Phosphohydrolases* / genetics
  • GTP Phosphohydrolases* / metabolism
  • Humans
  • Mitochondria* / metabolism
  • Mitochondrial Dynamics / physiology
  • Mitochondrial Proteins* / metabolism
  • Neurodegenerative Diseases* / metabolism

Substances

  • GTP Phosphohydrolases
  • Mitochondrial Proteins
  • MFN2 protein, human