Apoptosis is an important mechanism limiting cellular expansion in situations of excessive cell growth such as neoplasia or chronic inflammation. Mitochondria play a key role in stress induced apoptosis and provide an amplification loop of death receptor triggered apoptotic signals. The release of mitochondrial cytochrome c into the cytosol is a critical event in apoptosis. Cytochrome c activates oligomerization of apoptotic protease activating factor-1 (Apaf-1), an adapter protein that links the mitochondrial signal to activation of caspase-9, an enzyme involved in apoptosis. Inactivation of apoptosis signaling pathways as a result of mutations or epigenetic mechanisms has been demonstrated in cancer, autoimmunity, and in the pseudotumoral growth of rheumatoid synovium.