Details

Autor(en) / Beteiligte

• Sun, Yanyan
• Li, Tao
• Xie, Cuicui
• Xu, Yiran
• Zhou, Kai
• Rodriguez, Juan
• Han, Wei
• Wang, Xiaoyang
• Kroemer, Guido
• Modjtahedi, Nazanine
• Blomgren, Klas
• Zhu, Changlian

Titel

Haploinsufficiency in the mitochondrial protein CHCHD4 reduces brain injury in a mouse model of neonatal hypoxia-ischemia

Ist Teil von

• Cell death & disease, 2017-05, Vol.8 (5), p.e2781-e2781

Ort / Verlag

England: Nature Publishing Group

Erscheinungsjahr

2017

Quelle

MEDLINE

Beschreibungen/Notizen

• 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.