Cell death: insights into the ultrastructure of mitochondria.

An essential step in many forms of cell death is the release from mitochondria of "death effectors" which once in the cytoplasm activate signalling pathways leading to cellular demise. In this context mitochondria are known as regulators of cell death functioning as a node where signals are integrated. The discovery that alterations and remodelling of ultrastructural architecture of mitochondria are required to trigger the complete release of cytochrome c in the cytoplasm and the notion that mitochondrial architecture determines/influences the function of this organelle has fostered investigations on mitochondrial dynamics and on the machinery that regulates this process during cell death. In this review I shall summarize the current knowledge of mitochondrial inner membrane remodelling during cell death and discuss the role of mitochondrial proteins in governing structural alterations. I shall then discuss the role of the adaptor protein p66Shc as a regulator of mitochondrial metabolism during apoptosis.