Autophagy and mitophagy have been shown to occur in spinal cord injury (SCI). Bcl-2/E1B-19KD-interacting protein 3 (BNIP3) and its homologue, NIX, have been implicated in the regulation of mitophagy. The aim of this work was to characterize the mechanisms and role of BNIP3 in SCI-associated mitophagy. Our data showed that BNIP3, targeted to mitochondria, interacted with microtubule-associated protein 1A/1B-light chain 3 (LC3), which is targeted to autophagosomes, thus forming a mitochondria-BNIP3-LC3-autophagosome complex and resulting in mitophagy. Downregulation of BNIP3 by RNA interference strengthened the mitochondrial function and decreased cell death in spinal cord neurons under hypoxia. Particularly, BNIP3 knockdown significantly improved neurological recovery and the number of neuronal nuclei-positive cells post-SCI in rats. The present study demonstrated that BNIP3 interacts with LC3 to induce mitophagy, whereas its inhibition provided protective neuronal effects in SCI rat models both in vivo and in vitro.
Keywords: Bcl-2/E1B-19KD-interacting protein 3; NIX; hypoxia; mitophagy; spinal cord injury.