Other proteins released from Damaged Mitochondria, SMAC (Second Mitochondria-Derived Activator of Caspase)/ Diablo, Arts and Omi/HTRA2 (High Temperature Requirement Protein-A2), counteract the effect of IAPs (Inhibitor of Apoptosis Proteins), which normally bind and prevent activation of Caspase3. The interaction between Bcl family members, IAPs, SMAC and Omi/HTRA2 is central to the intrinsic Apoptosis pathway. Recent studies demonstrated that another nuclease, EndoG (Endonuclease-G), is specifically activated by Apoptotic stimuli and is able to induce nucleosomal fragmentation of DNA independently of Caspase and DFF (DNA-Fragmentation Factor)/ CAD (Caspase-Activated DNAse). EndoG is a mitochondrion-specific nuclease that translocates to the nucleus and cleaves chromatin DNA during Apoptosis. Another protein, AIF (Apoptosis Inducing Factor) has also been attributed a role in Apoptosis, becoming active upon translocation from Mitochondria to nuclei, where it initiates chromatin condensation and large-scale DNA fragmentation (). Endoplasmic reticulum stress also takes part in apoptosis by activating Caspase3 via Caspase12. Programmed cell death and its morphologic manifestation of Apoptosis is a conserved pathway that in its basic tenets appears operative in all metazoans. Apoptosis also operates in adult organisms to maintain normal cellular homeostasis. This is especially critical in long-lived mammals that must integrate multiple physiological as well as pathological death signals, which for example includes regulating the response to infectious agents. Gain and loss of function models of genes in the core Apoptotic pathway indicate that the violation of cellular homeostasis can be a primary pathogenic event that results in disease. Evidence indicates that insufficient Apoptosis can manifest as Cancer or Autoimmunity, while accelerated cell death is evident in Acute and Chronic Degenerative diseases, Immunodeficiency, and Infertility (Ref. 8 & 9).