RGD Reference Report - Cardioprotection by modulation of mitochondrial respiration during ischemia-reperfusion: role of apoptosis-inducing factor. - Rat Genome Database

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Cardioprotection by modulation of mitochondrial respiration during ischemia-reperfusion: role of apoptosis-inducing factor.

Authors: Xu, A  Szczepanek, K  Hu, Y  Lesnefsky, EJ  Chen, Q 
Citation: Xu A, etal., Biochem Biophys Res Commun. 2013 Jun 14;435(4):627-33. doi: 10.1016/j.bbrc.2013.05.033. Epub 2013 May 16.
RGD ID: 10053560
Pubmed: PMID:23685150   (View Abstract at PubMed)
DOI: DOI:10.1016/j.bbrc.2013.05.033   (Journal Full-text)

The transient, reversible blockade of electron transport (BET) during ischemia or at the onset of reperfusion protects mitochondria and decreases cardiac injury. Apoptosis inducing factor (AIF) is located within the mitochondrial intermembrane space. A release of AIF from mitochondria into cytosol and nucleus triggers caspase-independent cell death. We asked if BET prevents the loss of AIF from mitochondria as a mechanism of protection in the buffer perfused heart. BET during ischemia with amobarbital, a rapidly reversible inhibitor of mitochondrial complex I, attenuated a release of AIF from mitochondria into cytosol, in turn decreasing the formation of cleaved and activated PARP-1. These results suggest that BET-mediated protection may occur through prevention of the loss of AIF from mitochondria during ischemia-reperfusion. In order to further clarify the role of mitochondrial AIF in BET-mediated protection, Harlequin (Hq) mice, a genetic model with mitochondrial AIF deficiency, were used to test whether BET could still decrease cell injury in Hq mouse hearts during reperfusion. BET during ischemia protected Hq mouse hearts against ischemia-reperfusion injury and improved mitochondrial function in these hearts during reperfusion. Thus, cardiac injury can still be decreased in the presence of down-regulated mitochondrial AIF content. Taken together, BET during ischemia protects both hearts with normal mitochondrial AIF content and hearts with mitochondrial AIF deficiency. Although preservation of mitochondrial AIF content plays a key role in reducing cell injury during reperfusion, the protection derived from the BET is not fully dependent on AIF-driven mechanisms.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
AIFM1HumanMyocardial Reperfusion Injury  ISOAifm1 (Rattus norvegicus)protein:decreased expression:mitochondrion:RGD 
AIFM1HumanMyocardial Reperfusion Injury  ISOAifm1 (Mus musculus) RGD 
Aifm1RatMyocardial Reperfusion Injury  ISOAifm1 (Mus musculus) RGD 
Aifm1RatMyocardial Reperfusion Injury  IEP protein:decreased expression:mitochondrion:RGD 
Aifm1MouseMyocardial Reperfusion Injury  ISOAifm1 (Rattus norvegicus)protein:decreased expression:mitochondrion:RGD 
Aifm1MouseMyocardial Reperfusion Injury  IMP  RGD 

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Aifm1Ratresponse to ischemia NOTIEP  RGD 

Objects Annotated

Genes (Rattus norvegicus)
Aifm1  (apoptosis inducing factor, mitochondria associated 1)

Genes (Mus musculus)
Aifm1  (apoptosis-inducing factor, mitochondrion-associated 1)

Genes (Homo sapiens)
AIFM1  (apoptosis inducing factor mitochondria associated 1)


Additional Information