A moderate but not total decrease of mitochondrial membrane potential triggers apoptosis in neuron-like cells.
The effects of various degrees of perturbation of the mitochondrial membrane potential (mt delta psi) on apoptosis was investigated by intensified fluorescence digital-imaging microscopy on neuron-like cells, ND7. Mt delta psi was either decreased by 40% by the protonophore carbonyl cyanide p-trifluoromethoxyphenylhydrazone (FCCP 100 nM, 15 min) or completely collapsed (FCCP 10 microM, 60 min). A moderate decrease of mt delta psi induced a reduction of mitochondrial NADH, followed by exposure of phosphatidyl serine and then by chromatin condensation, 36% of nuclei being condensed 60 min after FCCP treatment. During these stages, mitochondrion morphology was fully preserved. In contrast, no chromatin condensation was observed after a rapid and total dissipation of mt delta psi. These results suggest that a partial decrease of mt delta psi would allow mitochondrial functions required to trigger apoptosis to be sustained.
Gautier
I
I
Institut Jacques Monod, UMR 7592, CNRS, Universités P6/P7, Paris, France.
Geeraert
V
V
Coppey
J
J
Coppey-Moisan
M
M
Durieux
C
C
D000818:Animals; D017304:Annexin A5 / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D002259:Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone / Q000494:pharmacology; D002462:Cell Membrane / Q000187:drug effects* / Q000378:metabolism; D002467:Cell Nucleus / Q000187:drug effects / Q000648:ultrastructure; D002478:Cells, Cultured / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D053938:DNA Fragmentation / Q000187:drug effects / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D016650:Fluorescein-5-isothiocyanate; D008564:Membrane Potentials / Q000187:drug effects* / Q000502:physiology; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D009243:NAD / Q000378:metabolism; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D010718:Phosphatidylserines / Q000378:metabolism; D051381:Rats
D017304:Annexin A5; D010718:Phosphatidylserines; D009243:NAD; D002259:Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone; D016650:Fluorescein-5-isothiocyanate