PINK1/Parkin mitophagy and neurodegeneration-what do we really know in vivo?

Curr Opin Genet Dev. 2017 Jun;44:47-53. doi: 10.1016/j.gde.2017.01.016. Epub 2017 Feb 16.


Mitochondria are essential organelles that provide cellular energy and buffer cytoplasmic calcium. At the same time they produce damaging reactive oxygen species and sequester pro-apoptotic factors. Hence, eukaryotes have evolved exquisite homeostatic processes that maintain mitochondrial integrity, or ultimately remove damaged organelles. This subject has garnered intense interest recently following the discovery that two Parkinson's disease genes, PINK1 and parkin, regulate mitochondrial degradation (mitophagy). The molecular details of PINK1/Parkin-induced mitophagy are emerging but much of our insight derives from work using cultured cells and potent mitochondrial toxins, raising questions about the physiological significance of these findings. Here we review the evidence supporting PINK1/Parkin mitophagy in vivo and its causative role in neurodegeneration, and outline outstanding questions for future investigations.

Publication types

  • Review

MeSH terms

  • Calcium / metabolism
  • Humans
  • Mitochondria / genetics
  • Mitochondria / pathology
  • Mitophagy / genetics
  • Nerve Degeneration / genetics*
  • Nerve Degeneration / pathology
  • Parkinson Disease / genetics*
  • Parkinson Disease / metabolism
  • Parkinson Disease / pathology
  • Protein Kinases / genetics*
  • Reactive Oxygen Species / metabolism
  • Ubiquitin-Protein Ligases / genetics*


  • Reactive Oxygen Species
  • Ubiquitin-Protein Ligases
  • parkin protein
  • Protein Kinases
  • PTEN-induced putative kinase
  • Calcium