The PTEN-induced putative kinase 1 (PINK1) gene encodes a serine/threonine protein kinase that plays a key role in mitochondrial quality control and cellular homeostasis. PINK1 is located on chromosome 1, p36, and is primarily associated with mitochondrial function and acts as a sensor of mitochondrial damage. When mitochondria are depolarized or stressed, PINK1 accumulates on the outer mitochondrial membrane and initiates the recruitment of the E3 ubiquitin ligase Parkin, which promotes mitophagy, the selective degradation of dysfunctional mitochondria. Mutations in the PINK1 gene are associated with autosomal recessive early-onset Parkinson's disease (PD), highlighting its critical role in neuronal survival. In addition to neurodegenerative diseases, PINK1 is involved in regulating apoptosis, oxidative stress responses, and immune signaling, making it a key target for the study of neurodegenerative diseases, cancer, and metabolic disorders.
Human PINK1 Adenoviral Particles are genetically engineered recombinant adenovirus designed to deliver the human PINK1 gene to target cells for overexpression studies. These particles take advantage of the high transduction efficiency and broad tropism of adenoviral vectors to ensure robust gene expression in both dividing and non-dividing cells, including neurons and primary cultures. Adenoviral backbones are optimized for improved safety and typically lack the E1/E3 regions, rendering the virus replication-deficient while maintaining high levels of transgene expression. Human PINK1 adenoviral particles are widely used to study the role of PINK1 in mitophagy, mitochondrial dynamics, and neuroprotection, as well as to model the pathogenesis of Parkinson's disease in vitro or in vivo.
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)
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United Kingdom
07/26/2022
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