BNIP3L/NIX-mediated mitophagy: Future directions in Alzheimer’s disease

Abstract

BCL2-interacting protein 3 like (BNIP3L) /Nip3-like protein X (NIX) is a mitochondrial outer membrane protein possessing mitophagic and pro-apoptotic properties. Mitochondrial dysfunction and subsequent mitophagy impairment are some of the early triggers for Alzheimer’s Disease (AD), which is a progressive neurodegenerative condition affecting memory, thinking, and behavior. AD is associated with mitochondrial protein impairment and mitophagy failure. A recent study showed downregulation in BNIP3L expression in response to stress hormone release during Alzheimer’s, and pretreatment with a BNIP3L enhancer of a corticosterone-exposed mouse upregulated mitophagy. This research proved that BNIP3L stimulation can be an effective therapeutic strategy against Alzheimer’s. However, BNIP3L-mediated mitophagy studies focused on Alzheimer’s have been relatively scarce, and expanding knowledge on its regulatory proteins will help lay a smoother road ahead for future Alzheimer’s research. In this review, we aim to summarize all the recent findings of the downstream proteins of BNIP3L, which play an indispensable role in inducing BNIP3L-mediated mitophagy effects. The review also explicates the significance of healthy mitochondria and normally functioning mitophagy in Alzheimer’s. Finally, the review states the implications of BNIP3L in other diseases, like cardiovascular conditions and cancer, underscoring the immense potential of this wonder protein.