22:T506,Mitophagy, a central process guarding mitochondrial quality, is commonly impaired in human diseases such as Parkinson's disease, but its impact in adaptive immunity remains unclear. The differentiation and survival of memory CD8⁺ T cells rely on oxidative metabolism, a process that requires robust mitochondrial quality control. Here, we found that Parkinson's disease patients have a reduced frequency of CD8⁺ memory T cells compared with healthy donors and failed to form memory T cells upon vaccination against COVID-19, highlighting the importance of mitochondrial quality control for memory CD8⁺ T cell formation. We further uncovered that regulators of mitophagy, including Parkin and NIX, were up-regulated in response to interleukin-15 (IL-15) for supporting memory T cell formation. Mechanistically, Parkin suppressed VDAC1-dependent apoptosis in memory T cells. In contrast, NIX expression in T cells counteracted ferroptosis by preventing metabolic dysfunction resulting from impaired mitophagy. Together, our results indicate that the mitophagy machinery orchestrates survival and metabolic dynamics required for memory T cell formation, as well as highlight a deficit in T cell-mediated antiviral responses in Parkinson's disease patients.23:T4cf,Hippo signaling acts as a tumor suppressor pathway by inhibiting the proliferation of adult stem cells and progenitor cells in various organs. Liver-specific deletion of Hippo pathway components in mice induces liver cancer development through activation of the transcriptional coactivators, YAP and TAZ, which exhibit nuclear enrichment and are activated in numerous types of cancer. The upstream-most regulators of Warts, the Drosophila ortholog of mammalian LATS1/2, are Kibra, Expanded, and Merlin. However, the roles of the corresponding mammalian orthologs, WWC1, FRMD6 and NF2, in the regulation of LATS1/2 activity and liver tumorigenesis in vivo are not fully understood. Here, we show that deletion of both Wwc1 and Nf2 in the liver accelerates intrahepatic cholangiocarcinoma (iCCA) development through activation of YAP/TAZ. Additionally, biliary epithelial cell-specific deletion of both Lats1 and Lats2 using a Sox9-Cre^ERT2 system resulted in iCCA development through hyperactivation of YAP/TAZ. These findings suggest that WWC1 and NF2 cooperate to promote suppression of cholangiocarcinoma development by inhibiting the oncogenic activity of YAP/TAZ via LATS1/2.

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