Dataset Information


PKC? replaces AMPK to regulate mitophagy: Another PEDF role on ischaemic cardioprotection.

ABSTRACT: Both decreased autophagy positive regulator AMP activated protein kinase (AMPK) level and promoted mitophagy are observed in oxygen-glucose deprivation (OGD) cardiomyocytes treated with pigment epithelium-derived factor (PEDF). This contradictory phenomenon and its underlying mechanisms have not been thoroughly elucidated. Our previous study reveals that PEDF increases the protein kinase C? (PKC?) and phospho-PKC? (p-PKC?) contents to promote mitophagy. Thus, we investigated the association between PKC? and mitophagy. Here we identify an interaction between PKC? and Unc-51-like kinase 1 (ULK1), essential component of mitophagy. Further analyses show this is a direct interaction within a domain of ULK1 that termed the serine/threonine-rich domain (S/T domain). Notably, a deletion mutant ULK1 that lacks the binding domain is defective in mediating PEDF-induced mitophagy. Furthermore, we demonstrate that ULK1 is phosphorylated at Ser317/555/777 and Raptor is also phosphorylated by phospho-PKC?. Phospho-ULK1 (p-ULK1) at these sites are all essential for PEDF-induced mitophagy and reduce the release of mitochondrial ROS and DNA. This study therefore identifies a previously uncharacterized interaction between the ULK1 and PKC? that can replace the AMPK-dependent mitophagy processes.


PROVIDER: S-EPMC6201373 | BioStudies | 2018-01-01T00:00:00Z

REPOSITORIES: biostudies

Similar Datasets

2017-01-01 | S-EPMC5601463 | BioStudies
1000-01-01 | S-EPMC5827378 | BioStudies
1000-01-01 | S-EPMC4210082 | BioStudies
1000-01-01 | S-EPMC4590606 | BioStudies
| S-EPMC3030664 | BioStudies
2020-01-01 | S-EPMC7653589 | BioStudies
2019-01-01 | S-EPMC6548903 | BioStudies
2019-01-01 | S-EPMC6642318 | BioStudies
2020-01-01 | S-EPMC7282624 | BioStudies
2019-01-01 | S-EPMC6668382 | BioStudies