MFNs-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 MFN1 and 2. Ubiquitinated MFN complexes 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.
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
Matrix
Inner Membrane
Inter-Membrane Space
Outer Membrane
