Microcin J25-Ga induces apoptosis in mammalian cells by inhibiting mitochondrial RNA-polymerase.
MccJ25, an antimicrobial peptide, was unable to cause apoptosis of COS-7 cells in spite of inducing reactive-oxygen species overproduction as well as cytochrome c release from isolated mitochondria. Surprisingly, MccJ25-Ga, an amidated variant of MccJ25 that displays similar anti-mitochondrial effects, did induce apoptosis in COS-7. The only difference found between the activities of these peptides was the unpredicted inhibition of mitochondrial RNA synthesis by MccJ25-Ga. These results led us to hypothesize that both mitochondrial RNA polymerase and mitochondrial membrane might be the molecular targets of MccJ25-Ga in mitochondria and this combined effect may lead to apoptosis.
Departamento de Bioquímica de la Nutrición, Instituto Superior de Investigaciones Biológicas, CONICET-UNT, Instituto de Química Biológica Dr Bernabe Bloj, San Miguel de Tucumán, Argentina.
María V
MV
Niklison-Chirou
Fernando
F
Dupuy
Lucila
L
Saavedra
Elvira
E
Hebert
Claudia
C
Banchio
Carlos
C
Minahk
Roberto D
RD
Morero
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001430:Bacteriocins / Q000494:pharmacology*; D019556:COS Cells; D002522:Chlorocebus aethiops; D012321:DNA-Directed RNA Polymerases / Q000037:antagonists & inhibitors*; D008928:Mitochondria / Q000201:enzymology*
D001430:Bacteriocins; C020411:microcin; D012321:DNA-Directed RNA Polymerases