VDAC1-mediated mitophagy

Contributor: Simone Patergnani
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Theorem

Information

Upon mitochondrial damage, Pink1 (PARK6) is stabilized by the TOM complex at outer mitochondrial membrane (OMM), where it dimerizes and becomes activated through auto-phosphorylation. Pink1 dimerization/activation recruits and phosphorylates Parkin (PRKN), which in turn promotes the ubiquitination of selected OMM proteins, such as VDAC1. Ubiquitinated VDAC1 are recognized by autophagy receptors (such as p62/SQSTM1) to initiate autophagosome formation and consequent mitochondrial degradation.

 

References:

Sekine S, Youle RJ. PINK1 import regulation; a fine system to convey mitochondrial stress to the cytosol. BMC Biol. 2018 Jan 10;16(1):2. doi:10.1186/s12915-017-0470-7. PMID: 29325568.

Eiyama A, Okamoto K. PINK1/Parkin-mediated mitophagy in mammalian cells. Curr Opin Cell Biol. 2015 Apr;33:95-101. doi: 10.1016/j.ceb.2015.01.002. Epub 2015 Feb 17. PMID: 25697963.

Geisler S, Holmström KM, Skujat D, Fiesel FC, Rothfuss OC, Kahle PJ, Springer W. PINK1/Parkin-mediated mitophagy is dependent on VDAC1 and p62/SQSTM1. Nat Cell Biol. 2010 Feb;12(2):119-31. doi: 10.1038/ncb2012. Epub 2010 Jan 24. PMID: 20098416.

 

Link to other Databases:

Reactome: https://reactome.org/PathwayBrowser/#/R-HSA-5205647&PATH=R-HSA-9612973,R-HSA-1632852,R-HSA-9663891

Mitochondrial processes

Demonstrative and biological steps

Dynamic view

Mito-location

Not Available/Not Relevant
    M
    Matrix
      IM
      Inner Membrane
        IMS
        Inter-Membrane Space
          OM
          Outer Membrane
            PMS
            Peri-Mitochondrial Space

              Dynamic mito-location