RGD Reference Report - Mitochondrial targeted cyclophilin d protects cells from cell death by peptidyl prolyl isomerization. - Rat Genome Database

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Mitochondrial targeted cyclophilin d protects cells from cell death by peptidyl prolyl isomerization.

Authors: Lin, DT  Lechleiter, JD 
Citation: Lin DT and Lechleiter JD, J Biol Chem 2002 Aug 23;277(34):31134-41.
RGD ID: 625503
Pubmed: PMID:12077116   (View Abstract at PubMed)
DOI: DOI:10.1074/jbc.M112035200   (Journal Full-text)

Cyclophilin D (CyPD) is thought to sensitize opening of the mitochondrial permeability transition pore (mPTP) based on the findings that cyclosporin A (CsA), a pseudo-CyPD substrate, hyperpolarizes the mitochondrial membrane potential (DeltaPsi) and inhibits apoptosis. We provide evidence that contrasts with this model. Using live cell imaging and two photon microscopy, we report that overexpression of CyPD desensitizes HEK293 and rat glioma C6 cells to apoptotic stimuli. By site-directed mutagenesis of CyPD that compromises peptidyl-prolyl cis-trans isomerase (PPIase) activity, we demonstrate that the mechanism involved in this protective effect requires PPIase activity. Furthermore, we show that, under resting conditions, DeltaPsi is hyperpolarized in CyPD wild type-overexpressing cells but not in cells overexpressing mutant forms of CyPD that lack PPIase activity. Finally, in glutathione S-transferase (GST) pull-down assays, we demonstrate that CyPD binding to the adenine nucleotide translocator (ANT), which is considered to be the core component of the mPTP, is not affected by the loss of PPIase activity. Collectively, our data suggest that CyPD should be viewed as a cell survival-signaling molecule and indicate a protective role of CyPD against apoptosis that is mediated by one or more targets other than the ANT.



Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
PpidRatnegative regulation of apoptotic process  IMP  RGD 
PpidRatprotein peptidyl-prolyl isomerization  IDA  RGD 
PpidRatregulation of mitochondrial membrane potential  IMP  RGD 
PpidRatresponse to oxidative stress  IMP  RGD 

Molecular Function

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Slc25a4Ratenzyme binding  IPIPpid (Rattus norvegicus) RGD 
PpidRatpeptidyl-prolyl cis-trans isomerase activity  IDA  RGD 
PpidRatprotein binding  IPISlc25a4 (Rattus norvegicus) RGD 

Objects Annotated

Genes (Rattus norvegicus)
Ppid  (peptidylprolyl isomerase D)
Slc25a4  (solute carrier family 25 member 4)


Additional Information