Caspase-independent apoptosis in Friend's erythroleukemia cells: role of mitochondrial ATP synthesis impairment in relocation of apoptosis-inducing factor and endonuclease G.
Mitochondria have emerged as the central components of both caspase-dependent and independent apoptosis signalling pathways through release of different apoptogenic proteins. We previously documented that parental and differentiated Friend's erythroleukemia cells were induced to apoptosis by oligomycin and H(2)O(2) exposure, showing that the energy impairment occurring in both cases as a consequence of a severe mitochondrial F(0)F(1)ATPsynthase inactivation was a common early feature. Here we provide evidence for AIF and Endo G mitochondrio-nuclear relocation in both cases, as a component of caspase-independent apoptosis pathways. No detectable change in mitochondrial transmembrane potential and no variation in mitochondrial levels of Bcl-2 and Bax are observed. These results point to the osmotic rupture of the mitochondrial outer membrane as occurring in response to cell exposure to the two energy-impairing treatments under conditions preserving the mitochondrial inner membrane. A critical role of the mitochondrial F(0)F(1)ATP synthase inhibition in this process is also suggested.
Comelli
Marina
M
Department of Biomedical Sciences and Technologies, University of Udine, 33100 Udine, Italy. marina.comelli@uniud.it
Genero
Nadia
N
Mavelli
Irene
I
D000255:Adenosine Triphosphate / Q000096:biosynthesis*; D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D051033:Apoptosis Inducing Factor / Q000378:metabolism*; D015153:Blotting, Western; D045744:Cell Line, Tumor; D004706:Endodeoxyribonucleases / Q000378:metabolism*; D053078:Membrane Potential, Mitochondrial / Q000502:physiology; D051379:Mice; D008928:Mitochondria / Q000378:metabolism*; D006180:Proton-Translocating ATPases / Q000037:antagonists & inhibitors*; D015398:Signal Transduction / Q000502:physiology*
D051033:Apoptosis Inducing Factor; D000255:Adenosine Triphosphate; D004706:Endodeoxyribonucleases; C052391:endonuclease G; D006180:Proton-Translocating ATPases