Most pathognomic sign of irreversible cell injury

Ref Robbins 9/e p50 Mitochondrial Damage and Dysfunction Mitochondria may be viewed as "mini-factories" that produce life-sustaining energy in the form of ATP. Not surprisingly, therefore, they are also critical players in cell injury and death (Fig. 1-16). Mitochondria are sensitive to many types of injurious stimuli, including hypoxia, chemi- cal toxins, and radiation. Mitochondrial damage may result in several biochemical abnormalities: * Failure of oxidative phosphorylation leads to progres- sive depletion of ATP, culminating in necrosis of the cell, as described earlier. * Abnormal oxidative phosphorylation also leads to the formation of reactive oxygen species, which have many deleterious effects, described below. * Damage to mitochondria is often associated with the formation of a high-conductance channel in the mito- chondrial membrane, called the mitochondrial permea- bility transition pore. The opening of this channel leads to the loss of mitochondrial membrane potentialand pH changes, fuher compromising oxidative phosphorylation. * The mitochondria also contain several proteins that, when released into the cytoplasm, tell the cell there is internal injury and activate a pathway of apoptosis, dis- cussed later.