Under hypoxia condition, nuclear-encoded mitochondrial pyruvate dehydrogenase beta gene expression is attenuated by promoting Nuclear Respiratory Factor 1 (NRF1) degradation, dampening hypoxia-mediated NRF1 degradation decreases the Warburg effect and promotes M1 polarization of TAM, promoting tumor cells to become more sensitive to apoptosis through a FADD-dependent manner 216. Here, NRF1 is linked to neoplasm.