| http://purl.uniprot.org/citations/24988326 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/24988326 | http://www.w3.org/2000/01/rdf-schema#comment | "AMP-activated protein kinase α1 knockout (prkaa1(-/-)) mice manifest splenomegaly and anemia. The underlying molecular mechanisms, however, remain to be established. In this study, we tested the hypothesis that defective autophagy-dependent mitochondrial clearance in prkaa1(-/-) mice exacerbates oxidative stress, thereby enhancing erythrocyte destruction. The levels of ULK1 phosphorylation, autophagical flux, mitochondrial contents, and reactive oxygen species (ROS) were examined in human erythroleukemia cell line, K562 cells, as well as prkaa1(-/-) mouse embryonic fibroblasts and erythrocytes. Deletion of Prkaa1 resulted in the inhibition of ULK1 phosphorylation at Ser555, prevented the formation of ULK1 and BECN1-PtdIns3K complexes, and reduced autophagy capacity. The suppression of autophagy was associated with enhanced damaged mitochondrial accumulation and ROS production. Compared with wild-type (WT) mice, prkaa1(-/-) mice exhibited a shortened erythrocyte life span, hemolytic destruction of erythrocytes, splenomegaly, and anemia, all of which were alleviated by the administration of either rapamycin to activate autophagy or Mito-tempol, a mitochondria-targeted antioxidant, to scavenge mitochondrial ROS. Furthermore, transplantation of WT bone marrow into prkaa1(-/-) mice restored mitochondrial removal, reduced intracellular ROS levels, and normalized hematologic parameters and spleen size. Conversely, transplantation of prkaa1 (-/-) bone marrow into WT mice recapitulated the prkaa1(-/-) mouse phenotypes. We conclude that PRKAA1-dependent autophagy-mediated clearance of damaged mitochondria is required for erythrocyte maturation and homeostasis."xsd:string |
| http://purl.uniprot.org/citations/24988326 | http://purl.org/dc/terms/identifier | "doi:10.4161/auto.29197"xsd:string |
| http://purl.uniprot.org/citations/24988326 | http://purl.uniprot.org/core/author | "Zhu H."xsd:string |
| http://purl.uniprot.org/citations/24988326 | http://purl.uniprot.org/core/author | "Xie Z."xsd:string |
| http://purl.uniprot.org/citations/24988326 | http://purl.uniprot.org/core/author | "Zhu Z."xsd:string |
| http://purl.uniprot.org/citations/24988326 | http://purl.uniprot.org/core/author | "Zhang M."xsd:string |
| http://purl.uniprot.org/citations/24988326 | http://purl.uniprot.org/core/author | "Viollet B."xsd:string |
| http://purl.uniprot.org/citations/24988326 | http://purl.uniprot.org/core/author | "Xing J."xsd:string |
| http://purl.uniprot.org/citations/24988326 | http://purl.uniprot.org/core/author | "Gaudry M."xsd:string |
| http://purl.uniprot.org/citations/24988326 | http://purl.uniprot.org/core/author | "Leclerc J."xsd:string |
| http://purl.uniprot.org/citations/24988326 | http://purl.uniprot.org/core/author | "Zou M.H."xsd:string |
| http://purl.uniprot.org/citations/24988326 | http://purl.uniprot.org/core/author | "Foretz M."xsd:string |
| http://purl.uniprot.org/citations/24988326 | http://purl.uniprot.org/core/date | "2014"xsd:gYear |
| http://purl.uniprot.org/citations/24988326 | http://purl.uniprot.org/core/name | "Autophagy"xsd:string |
| http://purl.uniprot.org/citations/24988326 | http://purl.uniprot.org/core/pages | "1522-1534"xsd:string |
| http://purl.uniprot.org/citations/24988326 | http://purl.uniprot.org/core/title | "PRKAA1/AMPKalpha1 is required for autophagy-dependent mitochondrial clearance during erythrocyte maturation."xsd:string |
| http://purl.uniprot.org/citations/24988326 | http://purl.uniprot.org/core/volume | "10"xsd:string |
| http://purl.uniprot.org/citations/24988326 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/24988326 |
| http://purl.uniprot.org/citations/24988326 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/24988326 |
| http://purl.uniprot.org/uniprot/#_Q13131-mappedCitation-24988326 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/24988326 |
| http://purl.uniprot.org/uniprot/#_Q5EG47-mappedCitation-24988326 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/24988326 |
| http://purl.uniprot.org/uniprot/#_O70405-mappedCitation-24988326 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/24988326 |
| http://purl.uniprot.org/uniprot/#_Q3TUQ7-mappedCitation-24988326 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/24988326 |
| http://purl.uniprot.org/uniprot/#_Q96E92-mappedCitation-24988326 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/24988326 |