ABSTRACT
Mitochondria play an important role in the process of cell death, which is now recognized as a complex continuum of mechanisms that include program cell death (apoptosis), necrosis, and autophagy (Kim et al. 2006). Apoptosis is a highly regulated and energy-dependent multistep biological process (Hetts 1998). Dysregulation of apoptosis-either abnormal initiation of the genetic self-termination program or failure to undergo apoptosis-causes various diseases, such as autoimmunity, neurodegeneration, heart disease, and cancer. Apoptosis generally operates via two pathways: (1) mitochondria-and (2) receptor-mediated. In the mitochondria-mediated pathway, an external insult acts on mitochondria with or without the action of proapoptotic proteins, to cause cytochrome c release from the mitochondria to the cytoplasm, which is accompanied by the loss of the mitochondrial membrane potential. Released cytochrome c interacts with apoptotic protease-activating factor 1 (Apaf-1), ATP, and procaspase 9 to form an apoptosome. Apoptosome then activates a cascade of cellular destruction events, beginning with the activation of death-execution eector caspases, such as caspase 3, and then the activation of downstream caspases, ultimately resulting in the hallmark of apoptosis, including condensation of nuclear and cytoplasmic contents, fragmentation of nuclear DNA, and membrane blebbing (Blankenberg 2008; Schon and Manfredi 2003).
