TCOF1 Regulates Tumor Cell Migration Through p53-Dependent Mitochondrial Homeostasis and F-Actin Dynamics

The deficiency of TCOF1 is closely associated with multiple cellular dysfunctions, but its function in mitochondrial homeostasis and cytoskeletal regulation remains unclear. First, our research revealed that TCOF1 deficiency significantly inhibits tumor cell migration, suggesting TCOF1 plays a crucial role in cellular motility. Further studies demonstrated that TCOF1 deficiency disrupts normal F-actin polymerization, compromises cytoskeletal structural integrity, and impairs the dynamic assembly of F-actin, thereby affecting cell morphology and motility functions. Additionally, TCOF1 deficiency leads to mitochondrial dysfunction characterized by aberrant energy metabolism. Mechanistically, TCOF1 deficiency decreased the protein levels of p53, subsequently affecting mitochondrial biogenesis and functional maintenance, suggesting TCOF1 may regulate mitochondrial homeostasis via a p53-dependent pathway. Collectively, our study reveals TCOF1's role in regulating tumor cell migration by influencing F-actin assembly and the p53-mitochondrial axis, playing a critical role in maintaining cytoskeletal dynamics and energy metabolism.