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

Sep 29, 2025Brain research

Clearance of damaged mitochondria by BNIP3L/NIX and possible roles in Alzheimer's disease

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Abstract

Downregulation of BNIP3L expression occurs in response to stress hormones during Alzheimer's Disease.

Mitochondrial dysfunction and mitophagy impairment are early triggers for Alzheimer's Disease.
Alzheimer's Disease is linked to mitochondrial protein impairment and failure of mitophagy.
Enhancing BNIP3L expression in corticosterone-exposed mice can increase mitophagy.
There is limited research on BNIP3L-mediated mitophagy specifically related to Alzheimer's.
Understanding the regulatory proteins of BNIP3L may facilitate future Alzheimer's research.
BNIP3L is also implicated in other diseases, including cardiovascular conditions and cancer.

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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.

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

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