Figure 2.

PARP1 leads to Bnip3-dependent mitochondrial damage. Cortical neuron cultures were exposed to the DNA alkylator MNNG (50 μm, 30 min) to cause pathological PARP1 activation. A, Both total cell homogenate and mitochondrial Bnip3 immunoreactivities were significantly enhanced 4 h after MNNG removal, in a manner reversed by the parp1^−/− genotype. *p < 0.05, **p < 0.01, compared with 0 MNNG controls; †p < 0.05, compared with the wild-type, MNNG-treated group, using ANOVA and the Student–Newman–Keuls post hoc test. B, Mitochondrial aggregation of JC-1 was reduced 4 h post-MNNG by increasing the cationic charge inside the matrix (red); monomeric JC-1 in the cytosol (green) was enhanced by MNNG. C, MNNG-induced mitochondrial depolarization was time dependent and was significantly reduced by deleting PARP1 or Bnip3. *p < 0.05, compared with 0 MNNG controls at the same time point; †p < 0.05, compared with the wild-type, MNNG-treated groups at the same time point. Data were analyzed using two-way ANOVA with Bonferroni's post hoc test. All data are reported as the mean ± SEM (n = 5–7). Scale bars, 25 μm.