title: Susceptibility of mitochondrial membranes to calcium and reactive oxygen species: implications for ischemic and toxic tissue damage.
abstract: In summary, with post ischemic and toxic injury, reactive oxygen species together with the Ca2+ activation of phospholipase A2, can produce injury to mitochondria. Reactive oxygen species damage mitochondria by enhancing membrane permeability and decreasing F1F0ATPase activity. With exposure of mitochondria to Ca2+ and reactive oxygen species, there is a synergistic injurious effect manifested by a marked increase in membrane permeability, a profound reduction in the electron transport chain respiratory function at site I, and a pronounced reduction in F1F0ATPase and adenine nucleotide translocase activities. Dibucaine, a PLA2 inhibitor, protected mitochondria exposed to Ca2+ and reactive oxygen species by preventing the electron transport defect, partially preserving F1F0ATPase activity, and restoring adenine nucleotide translocase activity to control levels. Mitochondrial function is important in generating ATP necessary for energy-dependent transport and restorative synthetic processes during the recovery state subsequent to ischemic or toxic injury. Understanding the cellular pathophysiology of ischemic and toxic mitochondrial damage will likely lead to the development of pharmacological approaches aimed at the enhancement of mitochondrial function and hence tissue survival and function after ischemic or toxic exposure.
authors.affiliation: Massachusetts General Hospital, Boston 02114.
authors.forename: C D
authors.initials: CD
authors.lastname: Malis
authors.forename: J V
authors.initials: JV
authors.lastname: Bonventre
mesh_terms: D000818:Animals; D002118:Calcium / Q000502:physiology*; D005609:Free Radicals; D006801:Humans; D007425:Intracellular Membranes / Q000378:metabolism*; D007511:Ischemia / Q000503:physiopathology*; D008928:Mitochondria / Q000378:metabolism*; D010100:Oxygen / Q000378:metabolism* / Q000633:toxicity
chemical_list: D005609:Free Radicals; D010100:Oxygen; D002118:Calcium