AMPK/PGC-1α and p53 modulate VDAC1 expression mediated by reduced ATP level and metabolic oxidative stress in neuronal cells

• VDAC1 expression is upregulated in neuronal cells under metabolic and oxidative stress, linking cellular energy status to mitochondrial apoptosis regulation. • Reduced ATP levels trigger VDAC1 upregulation via the AMPK/PGC-1α signaling pathway, revealing a novel energy-sensing mechanism. • p53 is identified as a transcription factor that directly regulates VDAC1 promoter activity during metabolic oxidative stress, providing a molecular link between stress response and apoptosis. • These findings highlight VDAC1 as a potential therapeutic target for diseases involving mitochondrial dysfunction, such as cancer and neurodegeneration.