Fig. 7. The hypothetical mechanism of BNIP3 phosphorylation-mediated mitophagy under hypoxia.

In response to moderate hypoxia (10% O₂ or early stages of 0.3% O₂), a generous amount of BNIP3 is phosphorylated at S60/T66 by JNK1/2, which blocks the conjugation of ubiquitin (Ub) to BNIP3, inducing mitophagy activation. In severe hypoxia (late stages of 0.3% O₂), JNK1/2 is inactivated and BNIP3 is dephosphorylated by PP1 or PP2A, which leads to the recruitment of ubiquitin to BNIP3 and its degradation via the ubiquitin-proteasome pathway, suppressing the induction of mitophagy.