The PINK1-Parkin pathway is involved in the regulation of mitochondrial remodeling process

Biochem Biophys Res Commun. 2009 Jan 16;378(3):518-23. doi: 10.1016/j.bbrc.2008.11.086. Epub 2008 Dec 3.

Abstract

The two Parkinson's disease (PD) genes, PTEN-induced kinase 1 (PINK1) and parkin, are linked in a common pathway which affects mitochondrial integrity and function. However, it is still not known what this pathway does in the mitochondria. Therefore, we investigated its physiological function in Drosophila. Because Drosophila PINK1 and parkin mutants show changes in mitochondrial morphology in both indirect flight muscles and dopaminergic neurons, we here investigated whether the PINK1-Parkin pathway genetically interacts with the regulators of mitochondrial fusion and fission such as Drp1, which promotes mitochondrial fission, and Opa1 or Marf, which induces mitochondrial fusion. Surprisingly, DrosophilaPINK1 and parkin mutant phenotypes were markedly suppressed by overexpression of Drp1 or downregulation of Opa1 or Marf, indicating that the PINK1-Parkin pathway regulates mitochondrial remodeling process in the direction of promoting mitochondrial fission. Therefore, we strongly suggest that mitochondrial fusion and fission process could be a prominent therapeutic target for the treatment of PD.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Drosophila Proteins / genetics
  • Drosophila Proteins / metabolism*
  • Drosophila melanogaster / genetics
  • Drosophila melanogaster / metabolism*
  • Drosophila melanogaster / ultrastructure
  • Membrane Fusion* / genetics
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism
  • Mitochondria / metabolism*
  • Mitochondria / ultrastructure
  • Mutation
  • Protein-Serine-Threonine Kinases / genetics
  • Protein-Serine-Threonine Kinases / metabolism*
  • Ubiquitin-Protein Ligases

Substances

  • Drosophila Proteins
  • Membrane Proteins
  • OPA1 protein, Drosophila
  • Ubiquitin-Protein Ligases
  • PINK1 protein, Drosophila
  • Protein-Serine-Threonine Kinases
  • park protein, Drosophila