Dihydroorotate dehydrogenase mutations lead to changes of protein and function in Miller syndrome
10.3969/j.issn.1671-8348.2018.07.020
- VernacularTitle:二氢乳清酸脱氢酶突变对米勒综合征患者体内蛋白及功能的研究
- Author:
Jingxian FANG
1
;
Lei CHEN
;
Jianying LIANG
;
Hong QIAN
;
Xiang TANG
Author Information
1. 南方医科大学口腔医院/广东省口腔医院儿童口腔科
- Keywords:
codon,nonsense;
mitochondria;
dihydroorotate dehydrogenase;
Miller syndrome;
protein instability
- From:
Chongqing Medicine
2018;47(7):933-937
- CountryChina
- Language:Chinese
-
Abstract:
Objective To observe the changes of corresponding proteins and function based on known clinical dihydroorotate dehydrogenase(DHODH) mutation types,i.e.,G202A,R346W and R135C in the patients with Miller syndrome.Methods HeLacell lines stably expressing Miller syndrome pathogenic mutation types G202A,R346W and R135C were established.Then the mitochondrial localization function,protein stability and enzyme activity of corresponding proteins were studied by the immunohistochemistry and mitochondrial layered positioning.Results The mitochondrial localization function of 3 kinds of DHODH mutation were not affected,which existed in the mitochondrial inner membrane after expression.The mutant G202A and R346W protein stability was reduced;the mutant R135C protein was stable,but base induced enzyme activity injury caused the deficiency of corresponding enzymatic activity.Conclusion The DHODH function injury may be related with the symptoms in Miller syndrome.
