ABSTRACT Cadmium (Cd) is a common environmental contaminant that poses significant concern due to its neurotoxic effects. Mitophagy and apoptosis are two critical processes involved in Cd‐induced central nervous system disorders, but the molecular mechanisms remain inadequately understood. Bcl2/adenovirus E1B 19 kDa protein‐interacting protein 3‐like (BNIP3L) is a crucial receptor protein that facilitates mitophagy. The study aimed to determine the precise mechanisms by which BNIP3L protects against Cd‐induced neurotoxicity in the rat cerebral cortex. Following BNIP3L knockdown in the cerebral cortices, 24 male Sprague−Dawley rats were exposed to 50 mg/L Cd for 90 days. Histological alterations in the cerebral cortex were assessed using Nissl staining and transmission electron microscopy. Mitophagy‐ and apoptosis‐related biomarkers were assessed using western blot analysis, immunofluorescence staining, and TUNEL staining. Our results revealed that BNIP3L knockdown increased COX IV expression, abolished the co‐localization of LC3 and TOMM20, inhibited mitophagosome formation, and exacerbated Cd‐induced cerebral cortex damage in rats. Moreover, BNIP3L knockdown exacerbated Cd‐induced apoptosis and upregulated the Bax/Bcl‐2 ratio, as well as the expression of cleaved caspase‐9 and cleaved caspase‐3. Collectively, our findings demonstrate that BNIP3L‐mediated mitophagy provides neuroprotection in the rat cerebral cortex by inhibiting mitochondrial pathway‐mediated apoptosis. Targeting mitophagy may have therapeutic promise for Cd‐induced neurotoxicity.
Wang et al. (Fri,) studied this question.
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