VDAC1 (Voltage Dependent Anion Channel 1)

The findings herein underscore the pivotal role of EV-derived VDAC1 in driving PTX resistance in GC through dual modulation of autophagy and mitophagy, mediated by the AMPK/mTOR signaling axis. Targeting EV-derived VDAC1 has emerged as a promising therapeutic strategy to counteract chemoresistance, providing a novel avenue for improving GC treatment outcomes.

Furthermore, the HK2 K144 mutation markedly enhances tumor cell glycolysis, fostering increased proliferation and migration both in vitro and in vivo. These findings underscore USP30 as a novel regulator of glycolysis in cancer cells via modulation of HK2 ubiquitination dynamics, suggesting its potential as a therapeutic target in cancer metabolism.

Functional experiments confirmed that silencing either genos inhibited cell proliferation, promoted apoptosis, reduced migration, and differentially affected ferroptosis. VDAC1 and VDAC2 are prognostic biomarkers and therapeutic targets in HCC, with genetic and immune interactions jointly influencing outcomes, supporting their potential for patient risk stratification and targeted or immune-based therapies.

CTHRC1 overexpression in SH-SY5Y cells promoted tau degradation and modulated network partner expression. CTHRC1 represents a central hub in cognitive function networks, suggesting therapeutic potential for neurodegenerative disorders.

Experiments performed in asymmetric KCl solution revealed that VA binding renders the channel predominantly anion selective, potentially disrupting cation fluxes and simultaneously affecting the transport of negatively charged metabolites. Taken together, these data represent a step forward into the comprehension of VDAC modulation as a potential therapeutic approach in cancer management.

Distinct pathogenic NLS mutations of FUS differentially regulate cellular stress responses through different mechanisms, contributing to ALS initiation and progression. Among these, FUSP525L promotes the formation of larger stress granules, whereas FUSR514S more readily activates the cellular ISR.

Collectively, our findings demonstrate that NaF activates the PINK1/Parkin-mediated mitophagy pathway; however, incomplete autophagic degradation leads to mitochondrial dysfunction and neuronal apoptosis, contributing to developmental neurotoxicity. Importantly, melatonin mitigates these adverse effects, suggesting its potential as a therapeutic agent for preventing fluoride-induced neurodevelopmental impairment through modulation of the PINK1/Parkin signaling axis.

Our study demonstrates that Ly6ghigh neutrophils play a critical role in immunosuppression and immune evasion through NET-induced apoptosis of CD8+ T cells. These findings underscore the importance of NETs and cathelicidin in BC lung metastasis, suggesting their potential as therapeutic targets in restoring antitumor immunity and in preventing metastatic progression.

Together, these findings identify VDAC1 as a direct p53 target whose expression, oligomerization, and pro-apoptotic activity are regulated by p53. They also reinforce the central role of VDAC1 oligomerization in apoptosis.

Site mutation of Cys607 in CAR-T cells abrogated DRP1 sulphenylation and restored mitochondrial structure and improves antitumor immunity. These findings define a novel redox-mediated mechanism of mitochondrial dysfunction in CAR-T cells exhaustion and identify the SO2-DRP1 axis as a potential therapeutic target to overcome metabolic exhaustion in CAR-T cell therapy.

Loss of these components amplifies PERK signaling and selectively kills cancer cells while sparing normal cells. These findings uncover a cancer-specific role of VDACs in ERAD regulation and calcium signaling, highlighting a therapeutically actionable vulnerability.