The author explains how hypoxia/ischemia is one of the major causes of mitochondrial dysfunction and neuronal cell death. SIRT1 silencing by lentiviral shRNA treatment during normoxic conditions in the absence of PARP1 activation caused Bnip3 upregulation, enhanced FoxO3a acetylation and increased binding of FoxO3a to the Bnip3 upstream promoter.