BNIP3L, also known as NIX, is a mitochondrial outer membrane protein that serves as a mitophagy receptor, playing a crucial role in maintaining mitochondrial quantity by eliminating dysfunctional or superfluous mitochondria through the autophagy machinery [3]. Mitophagy, the process it is involved in, is highly conserved and participates in various physiological and pathological processes. Genetic models, such as gene knockout (KO) mouse models, are valuable tools for studying BNIP3L's function.

In ischemic brains, degradation of BNIP3L by proteasomes leads to mitophagy deficiency. In bnip3l -/- mice, the protective effects of carfilzomib, a proteasome inhibitor that reverses BNIP3L degradation and restores mitophagy, are abolished, indicating BNIP3L's essential role in protecting against ischemic brain injury [1]. In glucocorticoid-treated hippocampal neurons, SH-SY5Y cells, and ICR mice, down-regulation of BNIP3L by glucocorticoids results in suppressed mitophagy, decreased synaptic density, and vesicle recycling. Pre-treatment with a NIX enhancer in corticosterone-exposed mice elevates mitophagy and synaptic density, improving spatial memory [2].

In conclusion, BNIP3L-mediated mitophagy is vital in multiple biological processes, especially in maintaining mitochondrial health and synaptic function. Studies using BNIP3L KO mouse models have significantly contributed to understanding its role in ischemic brain injury and glucocorticoid-induced synapse defects, providing potential therapeutic targets for these and related disease conditions.