Mitochondria at the Crossroads of Survival and Demise

Mitochondria are multifunctional organelles, and their structural and functional integrity is fundamental to cell life. In addition to their critical role in the production of ATP via oxidative phosphorylation and biosynthetic intermediates, mitochondria are also a major hub for cellular Ca2+ signaling. Moreover, mitochondria can actively or passively drive cellular demise. They can become the major source of reactive oxygen species (ROS) in pathological and physiological processes, and they are highly vulnerable to damage. Mitochondria represent a point of convergence for a variety of upstream cell death stimuli and undergo structural and functional remodeling with subsequent transmission of signals to downstream executioner proteins. The pathways include death stimuli such as dioxygen, metabolic perturbation, deprivation of survival factors, oxidative stress, Ca2+ overload, DNA damage, proteotoxic stress, and oncogene activation.