RGD Reference Report - Calcium/calmodulin-dependent protein kinase regulates the PINK1/Parkin and DJ-1 pathways of mitophagy during sepsis. - Rat Genome Database

Send us a Message
Submit Data |  Help |  Video Tutorials |  News |  Publications |  Download |  REST API |  Citing RGD |  Contact   
Search RGD Grant Resources Citing RGD About Us Contact Us
Genes Variants Community Projects QTLs Strains Markers Genome Information Ontologies Cell Lines References Download Submit Data
OntoMate (Literature Search) JBrowse (Genome Browser) Synteny Browser (VCMap) Variant Visualizer Multi-Ontology Enrichment (MOET) Gene-Ortholog Location Finder (GOLF) InterViewer (Protein-Protein Interactions) PhenoMiner (Quatitative Phenotypes) Gene Annotator OLGA (Gene List Generator) AllianceMine GViewer (Genome Viewer)
Aging & Age-Related Disease Cancer & Neoplastic Disease Cardiovascular Disease Coronavirus Disease Developmental Disease Diabetes Hematologic Disease Immune & Inflammatory Disease Infectious Disease Liver Disease Neurological Disease Obesity & Metabolic Syndrome Renal Disease Respiratory Disease Sensory Organ Disease
Find Models   new Genetic Models Autism Models Rat PhenoMiner (Quantitative Phenotypes) Chinchilla PhenoMiner Expected Ranges (Quantitative Phenotype) PhenoMiner Term Comparison Hybrid Rat Diversity Panel Phenotypes Phenotypes in Other Animal Models Animal Husbandry Strain Medical Records Phylogenetics Strain Availability Calendar Rats 101 Submissions Photo Archive
Pathways
Rat Community Forum Directory of Rat Laboratories Video Tutorials News RGD Publications RGD Presentations Archive Nomenclature Guidelines Resource Links Laboratory Resources Employment Resources

Calcium/calmodulin-dependent protein kinase regulates the PINK1/Parkin and DJ-1 pathways of mitophagy during sepsis.

Authors: Zhang, Xianghong  Yuan, Du  Sun, Qian  Xu, Li  Lee, Emma  Lewis, Anthony J  Zuckerbraun, Brian S  Rosengart, Matthew R 
Citation: Zhang X, etal., FASEB J. 2017 Jun 14. pii: fj.201601096RRR. doi: 10.1096/fj.201601096RRR.
RGD ID: 13432559
Pubmed: PMID:28615325   (View Abstract at PubMed)
PMCID: PMC5602905   (View Article at PubMed Central)
DOI: DOI:10.1096/fj.201601096RRR   (Journal Full-text)

During sepsis and shock states, mitochondrial dysfunction occurs. Consequently, adaptive mechanisms, such as fission, fusion, and mitophagy, are induced to eliminate damaged portions or entire dysfunctional mitochondria. The regulatory PINK1/Parkin and DJ-1 pathways are strongly induced by mitochondrial depolarization, although a direct link between loss of mitochondrial membrane potential (¿¿) and mitophagy has not been identified. Mitochondria also buffer Ca(2+), and their buffering capacity is dependent on ¿¿. Here, we characterize a role for calcium/calmodulin-dependent protein kinase (CaMK) I in the regulation of these mechanisms. Loss of ¿¿ with either pharmacologic depolarization or LPS leads to Ca(2+)-dependent mitochondrial recruitment and activation of CaMKI that precedes the colocalization of PINK1/Parkin and DJ-1. CaMKI is required and serves as both a PINK1 and Parkin kinase. The mechanisms operate in both immune and nonimmune cells and are induced in in vivo models of endotoxemia, sepsis, and hemorrhagic shock. These data support the idea that CaMKI links mitochondrial stress with the PINK1/Parkin and DJ-1 mechanisms of mitophagy.-Zhang, X., Yuan, D., Sun, Q., Xu, L., Lee, E., Lewis, A. J., Zuckerbraun, B. S., Rosengart, M. R. Calcium/calmodulin-dependent protein kinase regulates the PINK1/Parkin and DJ-1 pathways of mitophagy during sepsis.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Endotoxemia  ISOPrkn (Mus musculus)13432559; 13432559protein:increased expression:liver and mitochondrion (mouse)RGD 
Endotoxemia  IEP 13432559protein:increased expression:liver and mitochondrion (mouse)RGD 

Objects Annotated

Genes (Rattus norvegicus)
Prkn  (parkin RBR E3 ubiquitin protein ligase)

Genes (Mus musculus)
Prkn  (parkin RBR E3 ubiquitin protein ligase)

Genes (Homo sapiens)
PRKN  (parkin RBR E3 ubiquitin protein ligase)


Additional Information