The role of reactive oxygen species in mitochondrial permeability transition.
We have provided evidence that mitochondrial membrane permeability transition induced by inorganic phosphate, uncouplers or prooxidants such as t-butyl hydroperoxide and diamide is caused by a Ca(2+)-stimulated production of reactive oxygen species (ROS) by the respiratory chain, at the level of the coenzyme Q. The ROS attack to membrane protein thiols produces cross-linkage reactions, that may open membrane pores upon Ca2+ binding. Studies with submitochondrial particles have demonstrated that the binding of Ca2+ to these particles (possibly to cardiolipin) induces lipid lateral phase separation detected by electron paramagnetic resonance experiments exploying stearic acids spin labels. This condition leads to a disorganization of respiratory chain components, favoring ROS production and consequent protein and lipid oxidation.
Vercesi
A E
AE
Departamento de Bioquímica, Universidade Estadual de Campinas, Brazil.
Kowaltowski
A J
AJ
Grijalba
M T
MT
Meinicke
A R
AR
Castilho
R F
RF
D000818:Animals; D002118:Calcium / Q000378:metabolism; D006801:Humans; D007425:Intracellular Membranes / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism*; D008958:Models, Molecular; D018384:Oxidative Stress; D010539:Permeability; D017382:Reactive Oxygen Species / Q000378:metabolism*
D017382:Reactive Oxygen Species; D002118:Calcium