Human PINK1 adenoviral particles

Acute-on-chronic liver failure (ACLF) is a fatal syndrome with high short-term mortality. Increasing evidence suggests that apoptosis plays a crucial role in the progression of liver failure. PINK1 plays a crucial role in maintaining cell survival. However, the role and underlying mechanism of PINK1 in apoptosis in ACLF are not fully understood. Here, researchers found that PINK1 significantly improved ACLF, characterized by decreased aspartate aminotransferase (AST) and alanine aminotransferase (ALT), and improved gross and microscopic histopathological appearance of liver tissue. Meanwhile, PINK1 affected the expression of cleaved caspase-3 through mTORC2/AKT, and this effect was abolished after further intervention with Rictor or AKT. Overall, these findings suggest that PINK1 is involved in regulating multiple biological functions, including hepatocyte growth and apoptosis in ACLF, through the mTORC2/AKT signaling pathway.

First, the researchers examined the effects of PINK1 overexpression and knockdown on cell survival, respectively. L02 cells were transfected with adenovirus overexpressing PINK1 (Ad-PINK1), PINK1-specific siRNA (shPINK1), and a no-load control virus. CCK8 assays were performed to examine the effects of Ad-PINK1 and shPINK1 on H2O2-induced cell proliferation. CCK8 assays showed that PINK1 overexpression promoted the proliferation of L02 cells after H2O2 injury. In contrast, PINK1 knockdown significantly inhibited cell proliferation (Figure 1A). To explore the downstream targets of PINK1, the researchers examined changes in AKT phosphorylation levels. As shown in Figure 1B, PINK1 overexpression significantly enhanced the phosphorylation of Akt at Ser-473. This result was confirmed by immunostaining to detect phosphorylated Akt.

Figure 1. PINK1 regulates cell proliferation and enhances the phosphorylation level of Akt. (Yin X, et al., 2022)