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Mitochondria and cell death. Mechanistic aspects and methodological issues
P Bernardi1, L Scorrano, R Colonna
1CNR Unit for the Study of Biomembranes, Department of Biomedical Sciences, University of Padova, Italy. bernardi@civ.bio.unipd.it
Abstract:
Mitochondria are involved in cell death for reasons that go beyond ATP supply. A recent advance has been the discovery that mitochondria contain and release proteins that are involved in the apoptotic cascade, like cytochrome c and apoptosis inducing factor. The involvement of mitochondria in cell death, and its being cause or consequence, remain issues that are extremely complex to address in situ. The response of mitochondria may critically depend on the type of stimulus, on its intensity, and on the specific mitochondrial function that has been primarily perturbed. On the other hand, the outcome also depends on the integration of mitochondrial responses that cannot be dissected easily. Here, we try to identify the mechanistic aspects of mitochondrial involvement in cell death as can be derived from our current understanding of mitochondrial physiology, with special emphasis on the permeability transition and its consequences (like onset of swelling, cytochrome c release and respiratory inhibition); and to critically evaluate methods that are widely used to monitor mitochondrial function in situ.
Insights
Mitochondria play a crucial role in programmed cell death (apoptosis) by releasing key proteins. Understanding their complex involvement requires analyzing mitochondrial physiology and evaluating in situ monitoring methods.
Area of Science:
- Cell Biology
- Biochemistry
- Physiology
Background:
- Mitochondria's role in cell death extends beyond ATP production.
- Mitochondria release proteins like cytochrome c, crucial for apoptosis.
- The exact role of mitochondria in cell death (cause vs. consequence) is complex and debated.
Purpose of the Study:
- To elucidate the mechanistic aspects of mitochondrial involvement in cell death.
- To emphasize the role of mitochondrial permeability transition and its effects.
- To critically evaluate methods for monitoring mitochondrial function in situ.
Main Methods:
- Analysis of mitochondrial physiology.
- Focus on mitochondrial permeability transition.
- Evaluation of in situ monitoring techniques.
Main Results:
- Mitochondrial responses depend on stimulus type, intensity, and perturbed function.
- Mitochondrial permeability transition leads to swelling, cytochrome c release, and respiratory inhibition.
- Integration of mitochondrial responses is complex and difficult to dissect.
Conclusions:
- Mitochondria are central players in apoptosis through protein release.
- Mitochondrial permeability transition is a key event in cell death.
- Careful evaluation of in situ methods is necessary for accurate assessment of mitochondrial function in cell death.