title: Induction of neuronal mitophagy in acute spinal cord injury in rats.
abstract: Autophagy and up-regulation of autophagy-associated proteins microtubule-associated protein 1 light chain 3 (LC3) and Beclin-1 have been shown to occur in spinal cord injury (SCI). Bcl-2/E1B-19 K-interacting protein 3 (BNIP3) and Nip-like protein X (NIX, also known as BNIP3L) are mitochondrial BH3-only proteins that are implicated in mitophagy. In this study, we show that mitophagy is activated in the injured neurons, and hypoxia-inducible proteins BNIP3, NIX, and p53 are upregulated after SCI. Numerous autophagosomes containing damaged mitochondria (mitophagosomes) were found in the injured neurons 24 h after SCI in rats by transmission electron microscopy; mitophagy, therefore, had occurred. Hypoxia-inducible proteins BNIP3, NIX, and p53 were upregulated in spinal cord neurons in both a rat model of SCI and cultured primary spinal neurons exposed to hypoxia. BNIP3 and NIX were transcriptionally regulated mainly by hypoxia-inducible factor-1α as well as p53 in cultured spinal cord neurons. This study provides direct morphological and biochemical evidence for mitophagy in the damaged neural tissue after SCI.
authors: Department of Orthopedics, Xinqiao Hospital, The Third Military Medical University, Chongqing, 400037, China.
authors: Datang
authors: D
authors: Yu
authors: Mingfang
authors: M
authors: Li
authors: Bing
authors: B
authors: Ni
authors: Jiming
authors: J
authors: Kong
authors: Zhengfeng
authors: Z
authors: Zhang
mesh_terms: D000818:Animals; D015687:Cell Hypoxia; D004195:Disease Models, Animal; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism / Q000648:ultrastructure; D063306:Mitophagy; D009474:Neurons / Q000378:metabolism* / Q000648:ultrastructure*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013119:Spinal Cord Injuries / Q000378:metabolism* / Q000473:pathology*; D013904:Thoracic Vertebrae; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: D008565:Membrane Proteins; D008869:Microtubule-Associated Proteins; D016159:Tumor Suppressor Protein p53
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