A switchable role of neuronal BNIP3L/NIX in mitochondrial fate: fission or finish

in glutamatergic neurons of the basolateral amygdala selectively impairs contextual fear memory in mice, a phenotype rescued by both wild-type BNIP3L and a mitophagy-deficient BNIP3L mutant lacking the LC3-interacting region motif. Mechanistically, BNIP3L competitively binds AMP-activated protein kinase (AMPK), thereby relieving AMPK-dependent inhibitory phosphorylation of DNM1L/DRP1 (dynamin 1 like) at Ser637. This interaction promotes rapid mitochondrial fission, supporting synaptic energy availability during memory encoding. Together, these findings reveal a switchable function of BNIP3L in neurons, acting either to acutely regulate mitochondrial dynamics to meet energetic demand or to engage mitophagy when mitochondrial function becomes compromised.