title: Apoptosis is induced by decline of mitochondrial ATP synthesis in erythroleukemia cells.
abstract: Apoptosis is shown to occur in erythroleukemia cells after incubation with oligomycin, which specifically inactivates mitochondrial ATPsynthase. Energy charge and ATP content decline very early during the treatment. Mitochondrial respiration is dramatically decreased while lactate production results not modified. DNA fragmentation progressively increases starting one hour following oligomycin removal, while loss of plasma membrane integrity occurs with a much slower time-course. Similar effects are also shown in differentiation-induced erythroleukemia cells exposed to H(2)O(2). In this case, evidence is provided for the involvement of (*)OH generated by iron-catalyzed reactions in the mechanism by which H(2)O(2) impairs energy charge and induces apoptosis. We hypothesize a possible role played by interference with mitochondrial bioenergy through inactivation of mitochondrial ATPsynthase in the apoptosis triggered by oxidative stress under conditions in which cells undergo an iron overload-like status, as occurs in differentiation-induced erythroleukemia cells. These results point to the impairment of mitochondrial ATP synthesis and of energy charge as common early events critical for the execution of apoptosis, independently by the stimuli used for its induction: the specific inhibitor of mitochondrial ATPsynthase or H(2)O(2) exposure combined with the iron-enhancing differentiating treatment.
authors.affiliation: Department of Biomedical Sciences and Technologies, University of Udine, Italy. mcomelli@dstb.uniud.it
authors.forename: Marina
authors.initials: M
authors.lastname: Comelli
authors.forename: Francesca
authors.initials: F
authors.lastname: Di Pancrazio
authors.forename: Irene
authors.initials: I
authors.lastname: Mavelli
mesh_terms: D000244:Adenosine Diphosphate / Q000378:metabolism; D000249:Adenosine Monophosphate / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000096:biosynthesis / Q000378:metabolism*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002384:Catalysis; D045744:Cell Line, Tumor; D019069:Cell Respiration / Q000187:drug effects; D004734:Energy Metabolism / Q000187:drug effects; D006418:Heme / Q000096:biosynthesis; D006861:Hydrogen Peroxide / Q000037:antagonists & inhibitors / Q000494:pharmacology; D007501:Iron / Q000378:metabolism; D019344:Lactic Acid / Q000096:biosynthesis / Q000378:metabolism; D004915:Leukemia, Erythroblastic, Acute / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology*; D051379:Mice; D008928:Mitochondria / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D025261:Mitochondrial Proton-Translocating ATPases / Q000037:antagonists & inhibitors / Q000378:metabolism; D009840:Oligomycins / Q000494:pharmacology; D018384:Oxidative Stress / Q000187:drug effects; D010101:Oxygen Consumption / Q000187:drug effects; D013997:Time Factors
chemical_list: D009840:Oligomycins; D019344:Lactic Acid; D000249:Adenosine Monophosphate; D006418:Heme; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; D006861:Hydrogen Peroxide; D007501:Iron; D025261:Mitochondrial Proton-Translocating ATPases