title: Mitochondrial aggregation precedes cytochrome c release from mitochondria during apoptosis.
abstract: Mitochondria play a central role in apoptotic signaling pathways. Upon exposure to apoptotic stimuli, mitochondria release cytochrome c to the cytoplasm and activate caspase cascade leading to cell death. However, the events upstream of cytochrome c release are not fully understood. Here, we quantitate mitochondrial aggregation in situ using a novel laser scanning cytometry technique and reveal that mitochondria aggregate during apoptosis in a budding-like shape. The quantitative analysis reveals that mitochondrial aggregation is not inhibited by caspase-3 inhibitor ZEVD. Furthermore, bcl-x(L) transfection cannot suppress mitochondrial aggregation. However, overexpression of bcl-x(L) inhibits cytochrome c release from mitochondria. Therefore, mitochondrial aggregation is an event upstream of cytochrome c release during apoptosis. This mitochondrial aggregation was not observed in human leukemia H9 cells where apoptosis occurs in a mitochondria-independent fashion. Our studies imply that changes in the localization of mitochondria participate in the regulation of apoptosis through cytochrome c release.
authors.affiliation: Institute of Molecular and Cellular Biosciences, The University of Tokyo, Tokyo 113-0032, Japan.
authors.forename: Naomi
authors.initials: N
authors.lastname: Haga
authors.forename: Naoya
authors.initials: N
authors.lastname: Fujita
authors.forename: Takashi
authors.initials: T
authors.lastname: Tsuruo
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D019556:COS Cells; D053148:Caspase 3; D020169:Caspases / Q000502:physiology; D002460:Cell Line; D003574:Cytochrome c Group / Q000378:metabolism*; D005047:Etoposide / Q000494:pharmacology; D006801:Humans; D008928:Mitochondria / Q000502:physiology*
chemical_list: D003574:Cytochrome c Group; D005047:Etoposide; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases