ANT1 suppression inhibits the progression of colorectal cancer by suppressing PINK1/Parkin-mediated mitophagy

Mitochondrial dysfunction is closely related to tumor development. Adenine nucleotide translocator 1 (ANT1), which promotes ADP/ATP translocation across the inner mitochondrial membrane, is an important protein involved in mitochondrial function and plays a role in a variety of diseases, including cancer. However, its role in colorectal cancer (CRC) progression remains poorly understood. This study aims to explore the potential role of ANT1 in CRC and its relationship with mitophagy. Through immunohistochemical analysis, we find that ANT1 expression is significantly higher in the tumor tissues of CRC patients than in adjacent normal tissues and that its overexpression is associated with poor prognosis. Further experiments demonstrate that ANT1 knockdown significantly inhibited CRC cell proliferation, migration, and invasion and leads to mitochondrial dysfunction, increased ROS production, and apoptosis by suppressing mitophagy. Mechanistically, ANT1 knockdown downregulates the PINK1/Parkin pathway, thereby inhibiting mitophagy activity. Notably, PINK1 overexpression partially rescues the cellular dysfunction induced by ANT1 knockdown, suggesting a potential role for PINK1 in reversing the suppression of mitophagy. In vivo xenograft models also show that ANT1 knockdown markedly inhibits tumor growth. In conclusion, ANT1 may play a critical role in CRC progression by regulating mitophagy, providing a basis for its potential as a therapeutic target.