BCH445H1 Chapter Notes -Ubiquitin Ligase, Pink1, Mitophagy
Document Summary
In healthy cells pink 1 makes its way into the inner mitochondrial membrane through the tom 40 tim system via its stop transfer signal. When in the inner mitochondrial membrane it gets degraded by the rhomboid protease parl. In mitochondria with a destabilized membrane potential, pink1 gets integrated into the outer mitochondrial membrane likely through tom40 and sam. In this situation, parkin an e3 can ubiquitinate mitochondria and therefore target them for autophagic degradation. Cytosolic cleaved pink1 represses parkin translocation to mitochondria and mitophagy. Parkin - component of e3 ubiquitin ligase complex that mediates proteasomal degradation of targets. Pink152 accumulates at mom and then translocates to the cytosol. In the first paper they assume that pink1 and parkin can form a complex that induces mitophagy in the next they state that pink1 is able to inhibit parkin induced mitophagy by dissalowing for parkin import. Pink-1 phosphorylated mitofusin 2 is a parkin receptor for culling.
