BNIP3-mediated mitophagy attenuates hypoxic–ischemic brain damage in neonatal rats by inhibiting ferroptosis through P62–KEAP1–NRF2 pathway activation to maintain iron and redox homeostasis

Luo L, Deng L, Chen Y, Ding R, Li X. Identification of lipocalin 2 as a ferroptosis-related key gene associated with hypoxic-ischemic brain damage via STAT3/NF-κB signaling pathway. Antioxid (Basel). 2023;12:186.

Article  CAS  Google Scholar 

Finder M, Boylan GB, Twomey D, Ahearne C, Murray DM, Hallberg B. Two-year neurodevelopmental outcomes after mild hypoxic ischemic encephalopathy in the era of therapeutic hypothermia. JAMA Pediatr. 2020;174:48–55.

Article  PubMed  Google Scholar 

Niatsetskaya ZV, Sosunov SA, Matsiukevich D, Utkina-Sosunova IV, Ratner VI, Starkov AA, et al. The oxygen free radicals originating from mitochondrial complex I contribute to oxidative brain injury following hypoxia-ischemia in neonatal mice. J Neurosci: Off J Soc Neurosci. 2012;32:3235–44.

Article  CAS  Google Scholar 

Thatipamula S, Al Rahim M, Zhang J, Hossain MA. Genetic deletion of neuronal pentraxin 1 expression prevents brain injury in a neonatal mouse model of cerebral hypoxia-ischemia. Neurobiol Dis. 2015;75:15–30.

Article  CAS  PubMed  Google Scholar 

Su L, Zhang J, Gomez H, Kellum JA, Peng Z. Mitochondria ROS and mitophagy in acute kidney injury. Autophagy. 2023;19:401–14.

Article  CAS  PubMed  Google Scholar 

Zhang Y, Wang Y, Xu J, Tian F, Hu S, Chen Y, et al. Melatonin attenuates myocardial ischemia-reperfusion injury via improving mitochondrial fusion/mitophagy and activating the AMPK-OPA1 signaling pathways. J Pineal Res. 2019;66:e12542.

Article  PubMed  Google Scholar 

Tang YC, Tian HX, Yi T, Chen HB. The critical roles of mitophagy in cerebral ischemia. Protein Cell. 2016;7:699–713.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Baek SH, Noh AR, Kim KA, Akram M, Shin YJ, Kim ES, et al. Modulation of mitochondrial function and autophagy mediates carnosine neuroprotection against ischemic brain damage. Stroke 2014;45:2438–43.

Article  PubMed  PubMed Central  Google Scholar 

He G, Xu W, Tong L, Li S, Su S, Tan X, et al. Gadd45b prevents autophagy and apoptosis against rat cerebral neuron oxygen-glucose deprivation/reperfusion injury. Apoptosis. 2016;21:390–403.

Article  CAS  PubMed  Google Scholar 

Jiang T, Yu JT, Zhu XC, Zhang QQ, Tan MS, Cao L, et al. Ischemic preconditioning provides neuroprotection by induction of AMP-activated protein kinase-dependent autophagy in a rat model of ischemic stroke. Mol Neurobiol. 2015;51:220–9.

Article  CAS  PubMed  Google Scholar 

Wu X, Zheng Y, Liu M, Li Y, Ma S, Tang W, et al. BNIP3L/NIX degradation leads to mitophagy deficiency in ischemic brains. Autophagy. 2021;17:1934–46.

Article  CAS  PubMed  Google Scholar 

Tang D, Kang R, Berghe TV, Vandenabeele P, Kroemer G. The molecular machinery of regulated cell death. Cell Res. 2019;29:347–64.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Zhang M, Lin W, Tao X, Zhou W, Liu Z, Zhang Z, et al. Ginsenoside Rb1 inhibits ferroptosis to ameliorate hypoxic-ischemic brain damage in neonatal rats. Int Immunopharmacol. 2023;121:110503.

Article  CAS  PubMed  Google Scholar 

Gao M, Yi J, Zhu J, Minikes AM, Monian P, Thompson CB, et al. Role of mitochondria in ferroptosis. Mol Cell. 2019;73:354–363.e3.

Article  CAS  PubMed  Google Scholar 

Zheng J, Fang Y, Zhang M, Gao Q, Li J, Yuan H, et al. Mechanisms of ferroptosis in hypoxic-ischemic brain damage in neonatal rats. Exp Neurol. 2023;372:114641.

Article  PubMed  Google Scholar 

Dong B, Jiang Y, Shi B, Zhang Z, Zhang Z. Selenomethionine alleviates decabromodiphenyl ether-induced oxidative stress and ferroptosis via the NRF2/GPX4 pathway in the chicken brain. J Hazard Mater. 2023;465:133307.

Article  PubMed  Google Scholar 

Zhang L, Hu Z, Li Z, Lin Y. Crosstalk among mitophagy, pyroptosis, ferroptosis, and necroptosis in central nervous system injuries. Neural Regen Res. 2024;19:1660–70.

Article  PubMed  Google Scholar 

Zhang L, Lin Y, Bai W, Sun L, Tian M. Human umbilical cord mesenchymal stem cell-derived exosome suppresses programmed cell death in traumatic brain injury via PINK1/Parkin-mediated mitophagy. CNS Neurosci Ther. 2023;29:2236–58.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Song DD, Zhang TT, Chen JL, Xia YF, Qin ZH, Waeber C, et al. Sphingosine kinase 2 activates autophagy and protects neurons against ischemic injury through interaction with Bcl-2 via its putative BH3 domain. Cell Death Dis. 2017;8:e2912.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Chen JL, Wang XX, Chen L, Tang J, Xia YF, Qian K, et al. A sphingosine kinase 2-mimicking TAT-peptide protects neurons against ischemia-reperfusion injury by activating BNIP3-mediated mitophagy. Neuropharmacology. 2020;181:108326.

Article  CAS  PubMed  Google Scholar 

Sheng R, Zhang TT, Felice VD, Qin T, Qin ZH, Smith CD, et al. Preconditioning stimuli induce autophagy via sphingosine kinase 2 in mouse cortical neurons. J Biol Chem. 2014;289:20845–57.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Tan LL, Jiang XL, Xu LX, Li G, Feng CX, Ding X, et al. TP53-induced glycolysis and apoptosis regulator alleviates hypoxia/ischemia-induced microglial pyroptosis and ischemic brain damage. Neural Regen Res. 2021;16:1037–43.

Article  CAS  PubMed  Google Scholar 

Sheng R, Liu XQ, Zhang LS, Gao B, Han R, Wu YQ, et al. Autophagy regulates endoplasmic reticulum stress in ischemic preconditioning. Autophagy. 2012;8:310–25.

Article  CAS  PubMed  Google Scholar 

Wang X, Li M, Wang F, Mao G, Wu J, Han R, et al. TIGAR reduces neuronal ferroptosis by inhibiting succinate dehydrogenase activity in cerebral ischemia. Free Radic Biol Med. 2024;216:89–105.

Article  CAS  PubMed  Google Scholar 

Wang XX, Wang F, Mao GH, Wu JC, Li M, Han R, et al. NADPH is superior to NADH or edaravone in ameliorating metabolic disturbance and brain injury in ischemic stroke. Acta Pharmacol Sin. 2022;43:529–40.

Article  CAS  PubMed  Google Scholar 

Dai C, Wu B, Chen Y, Li X, Bai Y, Du Y, et al. Aagab acts as a novel regulator of NEDD4-1-mediated Pten nuclear translocation to promote neurological recovery following hypoxic-ischemic brain damage. Cell Death Differ. 2021;28:2367–84.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Deng J, Liao Y, Chen J, Chen A, Wu S, Huang Y, et al. N6-methyladenosine demethylase FTO regulates synaptic and cognitive impairment by destabilizing PTEN mRNA in hypoxic-ischemic neonatal rats. Cell Death Dis. 2023;14:820.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Gao K, Chen Y, Mo R, Wang C. Excessive BNIP3- and BNIP3L-dependent mitophagy underlies the pathogenesis of FBXL4-mutated mitochondrial DNA depletion syndrome. Autophagy. 2024;20:460–2.

Article  CAS  PubMed  Google Scholar 

Chen Y, Jiao D, Liu Y, Xu X, Wang Y, Luo X, et al. FBXL4 mutations cause excessive mitophagy via BNIP3/BNIP3L accumulation leading to mitochondrial DNA depletion syndrome. Cell Death Differ. 2023;30:2351–63.

Article  CAS  PubMed  Google Scholar 

Vara-Pérez M, Rossi M, Van den Haute C, Maes H, Sassano ML, Venkataramani V, et al. BNIP3 promotes HIF-1α-driven melanoma growth by curbing intracellular iron homeostasis. EMBO J. 2021;40:e106214.

Article  PubMed 

Comments (0)

No login
gif