Apoptosis-associated Derangement of Mitochondrial Function in Cells Lacking Mitochondrial DNA

摘要: U937 cells lacking mitochondrial DNA (ρ° cells) are auxotrophic for uridine and pyruvate, hypersensitive to hypoglycemic conditions, resistant antimycin A-induced apoptosis. In spite of their obvious metabolic defects, ρ° possess a normal transmembrane potential, as well near-normal capacity generate superoxide anion after menadione treatment. Similarly ρ+ controls, undergo apoptosis in response tumor necrosis factor-α plus cycloheximide. Detailed comparison the apoptotic process reveals essentially same sequence events. factor/cycloheximide, first lose potential (Δψm) then manifest late alterations, such generation reactive oxygen species fragmentation. Experiments involving isolated mitochondria from confirm that can be induced permeability transition, thought account pre-apoptotic Δψm disruption cells. Like mitochondria, contain pre-formed soluble factor is capable inducing chromatin condensation nuclei vitro . This released upon induction transition by calcium or specific ligand adenine nucleotide translocator atractyloside. conclusion, it appears all structures involved maintenance Δψm, factor(s), present thus controlled nuclear rather than genome. These findings underline contribution process.