Apoptotic pathways in LHON were extensively investigated and include a caspase-dependent pathway, via caspase-8/cleaved Bid/cyt c and activation of the apoptosome, formed by Apaf-1/cyt c/caspase-9, with final induction of caspase-3 [499,500]; as well as caspase independent transductions via apoptosis-inducing factor (AIF) and endonuclease G (EndoG) [501]. The gene discussed is ENDOG; the disease is Leber hereditary optic neuropathy.