mtDNA controls expression of the Death Associated Protein 3.
The Death Associated Protein 3 (DAP3), a GTP-binding constituent of the small subunit of the mitochondrial ribosome, is implicated in the TNFalpha and IFNgamma apoptotic pathways of the cell and is involved in the maintenance of the mitochondrial network. We have investigated the mitochondrial role of DAP3 by analyzing its mRNA and protein expression in transformed and non-transformed cell lines presenting various levels of mtDNA. The 3 mtDNA-less (rho degrees ) cell lines showed a complete absence of DAP3, whereas the mRNA expression was conserved. In HepG2 cells treated with increasing doses of ddCTP, the depletion of mtDNA was accompanied by the reduced expression of DAP3. However, the expression of the corresponding mRNA was maintained, suggesting the existence of a post-transcriptional mechanism responsible for the depletion of the DAP3. Compared to the parental cells, the 3 rho degrees cell lines displayed partial resistance to staurosporin-induced cell death. The absence of pro-apoptotic DAP3 in these mtDNA-less cells could explain their reduced apoptotic capacity. Our results suggest that the mtDNA content plays a role in cell apoptosis by mediating the expression of DAP3.
Jacques
Caroline
C
From INSERM, U694, F-49033 Angers, France. caroline.jacques@univ-angers.fr
Chevrollier
Arnaud
A
Loiseau
Dominique
D
Lagoutte
Laetitia
L
Savagner
Frédérique
F
Malthièry
Yves
Y
Reynier
Pascal
P
D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D051017:Apoptosis Regulatory Proteins / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism; D002460:Cell Line; D002478:Cells, Cultured; D004272:DNA, Mitochondrial / Q000235:genetics / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D005786:Gene Expression Regulation / Q000187:drug effects / Q000235:genetics; D006801:Humans; D012333:RNA, Messenger / Q000187:drug effects / Q000235:genetics; D016601:RNA-Binding Proteins; D012269:Ribosomal Proteins / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism; D019311:Staurosporine / Q000494:pharmacology; D016047:Zalcitabine / Q000494:pharmacology
D051017:Apoptosis Regulatory Proteins; C097041:DAP3 protein, human; D004272:DNA, Mitochondrial; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D012269:Ribosomal Proteins; D016047:Zalcitabine; D019311:Staurosporine