Alcohol and thiamine deficiency trigger differential mitochondrial transition pore opening mediating cellular death.

Accumulating evidence has shown that binge-type alcohol intake in mothers interferes with thiamine deficiency (TD) to promote the fetal alcohol syndrome (FAS). Developmental alcohol or TD exposures act either synergistically or separately to reproduce FAS features e.g. intrauterine growth retardation and related microcephaly characterized by extensive cellular death induced by one another neurotoxicant. However molecular and cellular mechanisms underlying apoptosis in both alcohol and TD toxicities are unknown. The current review addresses mechanisms of apoptosis underlying alcohol and TD toxicities for further understanding FAS pathology. This study indicates two different mitochondria pathways regulating cellular death: The first mechanism may engage alcohol which activates the c-subunit ring of the F0-ATP synthase to form MPT pore-dependent apoptosis; following the second mechanism, TD activates CyP-D translocation from mitochondrial matrix towards the mitochondrial inner membrane to form MPT pore-dependent necrosis. These studies shed light upon molecular and cellular mechanisms underlying apoptosis and necrosis in developemental brain disorders related to alcohol and thiamine deficiency, in hopes of developing new therapeutic strategies for FAS medication.