The role of HDAC3-interacting protein Pink1 in oxidative stress-mediated neuronal cell death

Abstract

[한글]

[영문]Even though histone deacetylase 3 (HDAC3) is shown to affect gene expression via the regulation of acetylation of histone substrates, the role of HDAC3 in well signaling is not well known. To further investigate the biological role of HDAC3 in apoptosis signaling, the yeast two-hybrid screening was performed and PINK1 was identified as a novel-HDAC3-interacting protein. Among the members of the class I HDACs, the kinase domain of PINK1 specifically interacts with the histone deacetylase domain of HDAC3. This study shows that PINK1 increases the activity of HDAC3 through blocking the c-terminal cleavage of HDAC3. Interestingly, co-expression of HDAC3 with PINK1 synergistically suppressed the oxidative stress-mediated apoptotic signal. However, over-expression of either one failed to inhibit H2O2-induced apoptosis. Thus the PINK1-HDAC3 complex is responsible for inhibiting H2O2-induced apoptosis. Consequently, the phosphorylation of HDAC3 reduces the acetylation of p53 and the transcription of the BAX gene. Furthermore, the HDAC3-PINK1 complex represses the translocalization of BAX into the mitochondria and the release of cytochrome C in the SH-SY5Y neuronal cell line. This study suggests that PINK1 protects neuronal cell death by enhancing the anti-apoptotic function of HDAC3.