FRAGILE MITOCHONDRIAL-DNA - THE MISSING LINK IN THE APOPTOTIC NEURONAL CELL-DEATH IN PARKINSONS-DISEASE

The oxidative stress theory, the mitochondrial (mt) hypothesis, and th e apoptosis hypothesis are proposed as the cause of neuronal cell deat h in Parkinson's disease (PD). However, the direct link between them h as remained unknown. Recently, the mt control of nuclear apoptosis is documented that collapse of mt transmembrane potential due to energy c risis leads to release of apoptotic protease activating-factors into c ytosol and subsequently nuclear DNA fragmentation. However, an endogen ous factor responsible for the energy crisis under physiological condi tions is missing. Here we report the missing factor as that mtDNA in t he striatum of a parkinsonian patient fragments into 134 types of dele ted pieces, being detected by the total detection system for mtDNA del etion, The system has documented that the mtDNA is extremely susceptib le to hydroxyl radical damage, hence to oxidative stress, enough to ca use the cellular energy crisis, The extensive fragility of mtDNA in br ain stem could link the oxidative stress up with the apoptotic neurona l cell-death of PD. (C) 1997 Academic Press.