Mitochondrial respiratory chain component NDUFA4: a promising therapeutic target for gastrointestinal cancer

Abstract Gastrointestinal cancer, one of the most common cancers, continues to be a major cause of mortality and morbidity globally. Accumulating evidence has shown that alterations in mitochondrial energy metabolism are involved in developing various clinical diseases. NADH dehydrogenase 1 alpha subcomplex 4 (NDUFA4), encoded by the NDUFA4 gene located on human chromosome 7p21.3, is a component of mitochondrial respiratory chain complex IV and integral to mitochondrial energy metabolism. Recent researchers have disclosed that NDUFA4 is implicated in the pathogenesis of various diseases, including gastrointestinal cancer. Aberrant expression of NDUFA4 leads to the alteration in mitochondrial energy metabolism, thereby regulating the growth and metastasis of cancer cells, indicating that it might be a new promising target for cancer intervention. This article comprehensively reviews the structure, regulatory mechanism, and biological function of NDUFA4. Of note, the expression and roles of NDUFA4 in gastrointestinal cancer including colorectal cancer, liver cancer, gastric cancer, and so on were discussed. Finally, the existing problems of NDUFA4-based intervention on gastrointestinal cancer are discussed to provide help to strengthen the understanding of the carcinogenesis of gastrointestinal cancer, as well as the development of new strategies for clinical intervention.