TY - JOUR
AU1 - Gao, Ju
AU2 - Qin, Siyue
AU3 - Jiang, Chang'an
AB - AbstractThe ubiquitin ligase Parkin and autophagic adapter protein p62 are known to function in a common pathway controlling mitochondrial autophagy (mitophagy). However, the evidence supporting that p62 is directly recruited by ubiquitinated proteins remains undetermined. Here, we demonstrate that mitochondrial fission factor (Mff) associates with Parkin and carbonyl cyanide m-chlorophenyl hydrazone treatment significantly increases the affinity of Parkin with Mff. After recruitment to depolarized mitochondria, Parkin mediates poly-ubiquitination of Mff at lysine 251. Replacement of lysine 251 by arginine (K251R) totally abrogates Parkin-stimulated ubiquitination of Mff. Subsequently, the ubiquitinated Mff promotes its association with p62. Mff knockout interferes with p62 translocation to damaged mitochondria. Only re-transfection of Mff WT, but not K251R mutant, rescues this phenotype. Furthermore, loss of Mff results in failure of Parkin translocation and final clearance of damaged mitochondria. Thus, our data reveal functional links among Mff, p62, and the selective autophagy of mitochondria, which are implicated in the pathogenesis of neurodegeneration diseases.
TI - Parkin-induced ubiquitination of Mff promotes its association with p62/SQSTM1 during mitochondrial depolarization
JF - Acta Biochimica et Biophysica Sinica
DO - 10.1093/abbs/gmv044
DA - 2015-07-01
UR - https://www.deepdyve.com/lp/oxford-university-press/parkin-induced-ubiquitination-of-mff-promotes-its-association-with-p62-i4G3ja3cRY
SP - 522
EP - 529
VL - 47
IS - 7
DP - DeepDyve
ER -