The mitochondrial pathway: Focus on shape changes

Abstract

Mitochondria are key participants in cell death. They amplify death signals by releasing proapoptotic proteins normally stored in their intermembrane space, such as cytochrome c. In recent years, cytochrome c release has been demonstrated to be not only highly regulated by the proteins of the Bcl-2 family, but also influenced by changes in mitochondrial shape, including remodeling of the cristae and fragmentation of the cytosolic network, both orchestrated by a large group of mitochondria-shaping proteins. We focus our attention in this chapter on the involvement of mitochondrial shape changes in apoptosis and on their regulatory mechanisms. In particular, we discuss the roles of the pro-fusion OPA1 protein and of the inner mitochondrial membrane rhomboid PARL on cristae remodeling and apoptosis in mammals, and on the relationship among Bcl-2 family members, mitochondrial fragmentation, and cell death. These results open the possibility to modulate mitochondrial morphological changes in order to influence apoptosis and thus to intervene in the natural history of human diseases, from neurodegeneration to cancer.