ANT1 suppression inhibits the progression of colorectal cancer by suppressing PINK1/Parkin‑mediated mitophagyOA
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 cancers.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 inhibits 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.
Jin Ji;Mingrui Jiang;Shantanu Baral;Qiannan Sun;Dong Tang;Wei Wang;Jun Ren;Daorong Wang
Northern Jiangsu People’s Hospital Affiliated to Yangzhou University,Yangzhou 225001,China General Surgery Institute of Yangzhou,Yangzhou University,Yangzhou 225001,China Yangzhou Key Laboratory of Basic and Clinical Transformation of Digestive and Metabolic Diseases,Yangzhou 225001,ChinaNorthern Jiangsu People’s Hospital Affiliated to Yangzhou University,Yangzhou 225001,China General Surgery Institute of Yangzhou,Yangzhou University,Yangzhou 225001,China Yangzhou Key Laboratory of Basic and Clinical Transformation of Digestive and Metabolic Diseases,Yangzhou 225001,ChinaNorthern Jiangsu People’s Hospital Affiliated to Yangzhou University,Yangzhou 225001,China General Surgery Institute of Yangzhou,Yangzhou University,Yangzhou 225001,China Yangzhou Key Laboratory of Basic and Clinical Transformation of Digestive and Metabolic Diseases,Yangzhou 225001,ChinaGeneral Surgery Institute of Yangzhou,Yangzhou University,Yangzhou 225001,China Yangzhou Key Laboratory of Basic and Clinical Transformation of Digestive and Metabolic Diseases,Yangzhou 225001,China Medical Experimental Research Center,Northern Jiangsu People’s Hospital,Yangzhou 225001,ChinaNorthern Jiangsu People’s Hospital Affiliated to Yangzhou University,Yangzhou 225001,China General Surgery Institute of Yangzhou,Yangzhou University,Yangzhou 225001,China Yangzhou Key Laboratory of Basic and Clinical Transformation of Digestive and Metabolic Diseases,Yangzhou 225001,ChinaNorthern Jiangsu People’s Hospital Affiliated to Yangzhou University,Yangzhou 225001,China General Surgery Institute of Yangzhou,Yangzhou University,Yangzhou 225001,China Yangzhou Key Laboratory of Basic and Clinical Transformation of Digestive and Metabolic Diseases,Yangzhou 225001,ChinaNorthern Jiangsu People’s Hospital Affiliated to Yangzhou University,Yangzhou 225001,China General Surgery Institute of Yangzhou,Yangzhou University,Yangzhou 225001,China Yangzhou Key Laboratory of Basic and Clinical Transformation of Digestive and Metabolic Diseases,Yangzhou 225001,ChinaNorthern Jiangsu People’s Hospital Affiliated to Yangzhou University,Yangzhou 225001,China General Surgery Institute of Yangzhou,Yangzhou University,Yangzhou 225001,China Yangzhou Key Laboratory of Basic and Clinical Transformation of Digestive and Metabolic Diseases,Yangzhou 225001,China
医药卫生
adenine nucleotide translocator 1colorectal cancermitophagyParkinPINK1
《Acta Biochimica et Biophysica Sinica》 2026 (5)
P.1083-1101,19
supported by a grant from the Jiangsu Provincial Health and Wellness Commission Medical Research Key Projects(No.ZD2022047).
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