ABSTRACT
E-mail: huveyda@sabanciuniv.edu Departmental Communication: Jeremy Ryan, Department of Medical Oncology,
Dana-Farber Cancer Institute, 44 Binney St, Boston, MA, 02115, USA E-mail: Jeremy_Ryan@dfci.harvard.edu
Apoptosis or programmed cell death is a fundamental process for embryogenesis, tissue homeostasis and prevention of oncogenesis. Dysregulated apoptosis contributes to the pathogenesis of many human diseases, such as cancer, diabetes and neurodegenerative disorders. Th e extrinsic or death receptor-mediated and mitochondrial apoptotic pathways are two main apoptosis pathways in mammalian cells. Th e most critical step of apoptosis is the release of prodeath proteins including cytochrome c from mitochondria through permeabilization of outer mitochondrial membrane. Smac/DIABLO, AIF, HtrA2 and ARTS are among the other prodeath molecules released from mitochondria. Bcl-2 protein family members act as major regulators of apoptosis by controlling mitochondrial permeabilization. Th eir function is dictated by protein-protein interactions as a result selective binding patterns of BH3-only proteins with antiapoptotic Bcl-2 proteins. Multidomain proapoptotic Bcl-2 proteins Bax and Bak are crucial for
mitochondrial permeabilization and they facilitate the release of cytochrome c from mitochondria by forming pores in the outer mitochondrial membrane. Currently, there are two diff erent models explaining Bax and Bak activation upstream of cytochrome c release. In addition, mitochondrial remodeling by Opa1 and Parl also contributes to apoptosis by controlling mitochondrial cristae junctions. In this chapter we briefl y address these concepts to help in understanding the mechanisms of apoptosis regulation by mitochondria. A better understanding of these pathways would allow us to develop novel therapeutic tools for human diseases and to improve preventive measures targeting human health.
