Other
12 Authors
- Li T,
- Xu Y,
- Kroemer G,
- Blomgren K,
- Sun Y,
- Han W,
- Zhu C,
- Wang X,
- Modjtahedi N,
- Rodriguez J,
- Zhou K,
- Xie C
| First Author | Sun Y | Year | 2017 |
| Journal | Cell Death Dis | Volume | 8 |
| Issue | 5 | Pages | e2781 |
| PubMed ID | 28492551 | Mgi Jnum | J:319273 |
| Mgi Id | MGI:6863451 | Doi | 10.1038/cddis.2017.196 |
| Citation | Sun Y, et al. (2017) Haploinsufficiency in the mitochondrial protein CHCHD4 reduces brain injury in a mouse model of neonatal hypoxia-ischemia. Cell Death Dis 8(5):e2781 |
| abstractText | Mitochondria contribute to neonatal hypoxic-ischemic brain injury by releasing potentially toxic proteins into the cytosol. CHCHD4 is a mitochondrial intermembrane space protein that plays a major role in the import of intermembrane proteins and physically interacts with apoptosis-inducing factor (AIF). The purpose of this study was to investigate the impact of CHCHD4 haploinsufficiency on mitochondrial function and brain injury after cerebral hypoxia-ischemia (HI) in neonatal mice. CHCHD4(+/-) and wild-type littermate mouse pups were subjected to unilateral cerebral HI on postnatal day 9. CHCHD4 haploinsufficiency reduced insult-related AIF and superoxide dismutase 2 release from the mitochondria and reduced neuronal cell death. The total brain injury volume was reduced by 21.5% at 3 days and by 31.3% at 4 weeks after HI in CHCHD4(+/-) mice. However, CHCHD4 haploinsufficiency had no influence on mitochondrial biogenesis, fusion, or fission; neural stem cell proliferation; or neural progenitor cell differentiation. There were no significant changes in the expression or distribution of p53 protein or p53 pathway-related genes under physiological conditions or after HI. These results suggest that CHCHD4 haploinsufficiency afforded persistent neuroprotection related to reduced release of mitochondrial intermembrane space proteins. The CHCHD4-dependent import pathway might thus be a potential therapeutic target for preventing or treating neonatal brain injury. |
