毛囊鱼鳞病是一种遗传性角化异常性皮肤病，针对皮肤角化异常机制研究将有助于我们在分子生物学层面对此类疾病发病机制的理解。前期研究中，我们利用全外显子组及Sanger测序发现该病致病基因为MBTPS1和MBTPS2基因，发现MBTPS1基因在线粒体内表达，该基因通过ETFB调控线粒体功能，调节甘油三酯代谢、线粒体氧化磷酸化及呼吸链电子传递。同时我们在mbtps1基因沉默的斑马鱼疾病模型和患者皮损中，发现该基因缺陷导致胆固醇代谢、溶酶体及线粒体异常。本项目拟研究MBTPS1与ETFB在线粒体的结合位点及作用方式， MBTPS1基因变异对ETF、呼吸链复合体和线粒体有氧呼吸的影响，并研究其对线粒体异常、脂质堆积以及皮肤角化异常的影响及其可能机制。同时研究斑马鱼疾病模型和患者皮损中活性氧以及脂质代谢变化，明确该基因变异对呼吸链电子传递和脂质代谢的影响，从而研究其对皮肤角化异常影响的可能机制。

Ichthyosis follicularis is an hereditary cutaneous disorders of keratinization , the research of the mechanism about keratinization anomalies in the skin will help us to understand the pathogenesis of such diseases at the molecular level. In the previous study, we found that the causative genes of the disease are MBTPS1 and MBTPS2 gene by the whole exome sequencing and Sanger sequencing. We found that MBTPS1 gene localized to mitochondria of Hela cells and HaCaT cells. MBTPS1 gene regulates mitochondrial function, triglyceride metabolism, mitochondrial oxidative phosphorylation and respiratory chain electron transport via ETFB. At the same time, we found that the gene defect led to abnormalities of cholesterol metabolism, lysosome and mitochondrion in zebrafish disease model and patient lesions. This project intends to study the mitochondrial binding site and mechanism of MBTPS1 and ETFB in HaCaT cells and Hela cells, the effect of MBTPS1 gene mutation on ETF, respiratory chain complex and mitochondrial aerobic respiration, and to study its effect on mitochondrial abnormalities as well as the mechanism in keratinization anomalies. At the same time, we studied the changes of reactive oxygen species and lipid metabolism in the zebrafish disease model and the patient lesions, and clarified the influence of this gene mutation on the respiratory chain electron transport and the lipid metabolism, so as to study its possible mechanism of keratinization anomalies.