Previous studies have demonstrated that reprogramming the SIRT3-COX4I2 axis can reduce the progression of osteoarthritis.[45] Studies have revealed that hypoxia-inducible factor-1 controls the expression of COX4 subunits by triggering the transcription of COX4I2, thus manipulating the activity of the COX family, ATP synthesis, and reactive oxygen species generation. The gene discussed is COX4I2; the disease is osteoarthritis.