Impairment of the autophagy-lysosome pathway is implicated with the changes in a-synuclein and mitochondrial dysfunction observed in @entity191 ( @entity191 ). Damaged mitochondria accumulate @entity193 , which then recruits parkin, resulting in ubiquitination of mitochondrial proteins. These can then be bound by the autophagic proteins @entity16402 / @entity16402 and @entity21684 , resulting in degradation of mitochondria by mitophagy. Mutations in @entity193 and parkin genes are a cause of @entity191 . We found a significant increase in the expression of @entity16402 / @entity16402 mRNA and protein following mitophagy induction in @entity1 @entity521 SH-SY5Y cells. @entity16402 protein not only accumulated on mitochondria, but was also greatly increased in the cytosol. Increased @entity16402 /SQSMT1 expression was prevented in @entity193 knock-down cells, suggesting increased @entity16402 expression was a consequence of mitophagy induction. The transcription factors @entity13791 and @entity29630 , which play roles in mitochondrial and lysosomal biogenesis, respectively, can regulate @entity16402 /SQSMT1. We report that both @entity13791 and @entity29630 translocate to the nucleus following mitophagy induction and that the increase in @entity16402 mRNA levels was significantly impaired in cells with @entity13791 or @entity29630 knockdown. @entity29630 translocation also increased expression of itself and lysosomal proteins such as glucocerebrosidase and @entity10815 following mitophagy induction. We also report that cells with increased @entity29630 protein have significantly higher @entity6217 mRNA levels, a regulator of mitochondrial biogenesis, resulting in increased mitochondrial content. Our data suggests that @entity29630 is activated following mitophagy to maintain autophagy-lysosome pathway and mitochondrial biogenesis. Therefore, strategies to increase @entity29630 may improve both the clearance of a-synuclein and mitochondrial dysfunction in @entity191 . Damaged mitochondria are degraded by the autophagy-lysosome pathway and is termed mitophagy. Following mitophagy induction, the transcription factors @entity13791 and @entity29630 translocate to the nucleus, inducing the transcription of genes encoding for autophagic proteins such as @entity16402 , as well as lysosomal and mitochondrial proteins. We propose that these events maintain autophagic flux, replenish lysosomes and replace mitochondria.

Mitochondrial and lysosomal biogenesis are activated following XXXX /parkin-mediated mitophagy.

@entity1 :: ('9606', 'Species') :: ['human'] @entity10815 :: ('1509', 'Gene') :: ['cathepsin D'] @entity29630 :: ('7942', 'Gene') :: ['TFEB'] @entity16402 :: ('8878', 'Gene') :: ['p62', 'SQSTM1'] @entity191 :: ('MESH:D010300', 'Disease') :: ['familial PD', "Parkinson's disease", 'PD'] @entity13791 :: ('4780', 'Gene') :: ['Nrf2'] @entity193 :: ('65018', 'Gene') :: ['PINK1'] @entity6217 :: ('10891', 'Gene') :: ['PGC-1a'] @entity521 :: ('MESH:D009447', 'Disease') :: ['neuroblastoma'] @entity21684 :: ('84557', 'Gene') :: ['LC3']
@entity193 :: (65018,Gene) :: ['PINK1']
