Oxidative cell death: the mitochondrion

Mitochondria integrate signalling processes which ensure cellular well-being or which may culminate in cell death. They are a central target in diseases (e.g. Wilson disease), intoxication (e.g. acetaminophen) or pathological situations (e.g. ischemia/reperfusion) which are accompanied or characterized by excessive oxidative stress.

Structural and molecular alterations of the mitochondrial membrane system appear to be the most critical factors in these detrimental processes and cell death is (almost) uniformly accompanied by an increase in mitochondrial membrane permeability. Whereas the permeabilization of the mitochondrial inner membrane is partial and may be reversible, the outer membrane frequently becomes irreversibly ruptured, culminating in the release of soluble inter-membrane space proteins.

The mechanisms accounting for mitochondrial membrane permeabilization are a matter of debate. Under oxidative stress conditions, one mode is the so called permeability transition (PT). It involves a pore complex leading to structural transitions of the mitochondria and finally to mitochondrial outer membrane permeabilization. A plethora of distinct stimuli can trigger PT. Whether the resulting mitochondria are all equally damaged or whether different stages of damage exist is of particular importance with respect to the ongoing discussion about the implication of PT in distinct cell death scenarios.

One fundamental problem in this aspect is the limited methodology to resolve this heterogeneity and thus the ability to clarify the reasons why some organelles appear more affected and vulnerable than others. 

Oxidative stress induces structural abnormalities in rat liver mitochondria isolated from an animal model for chronic oxidative stress (i.e. the LEC rat, Cooperation with AG Summer).
Structural abnormalities in mitochondria in liver tissue subjected to oxidative stress by ischemia/reperfusion treatments.