中国科学院遗传与发育生物学研究所Shunji Jia等研究人员合作开发出，线粒体功能异常COXPD4综合征的斑马鱼tufm突变模型。2024年5月31日，《遗传学报》在线发表了这项成果。

据研究人员介绍，由于线粒体在产生细胞能量方面的核心作用，线粒体功能障碍是导致多种临床异质性疾病的关键因素，而且往往是严重的疾病。众所周知，TUFM基因突变可导致联合氧化磷酸化缺乏症 4（COXPD4），这是一种罕见的线粒体疾病，其特征是线粒体呼吸链（MRC）复合物全面定量缺乏。建立一个可靠的COXPD4动物模型，对于阐明TUFM在疾病发病机制中的作用和机制以及改善其医疗管理至关重要。

研究人员构建了一种斑马鱼tufm^-/-突变体，该突变体与COXPD4综合征非常相似，表现出线粒体蛋白翻译受损、线粒体氧化磷酸化（OXPHOS）缺陷和三羧酸（TCA）循环代谢显著抑制。利用这种COXPD4斑马鱼模型，研究人员全面验证了TUFM突变的临床相关性，并确定probucol是治疗COXPD4的一种很有前景的方法。这些数据为了解线粒体疾病和开发有效的治疗方法提供了宝贵的见解。

附：英文原文

Title: A zebrafish tufm mutant model for the COXPD4 syndrome of aberrant mitochondrial function

Author: Jihua Yao a, Shunji Jia c

Issue&Volume: 2024/05/31

Abstract: Mitochondrial dysfunction is a critical factor leading to a wide range of clinically heterogeneous and often severe disorders due to its central role in generating cellular energy. Mutations in the TUFM gene are known to cause combined oxidative phosphorylation deficiency 4 (COXPD4), a rare mitochondrial disorder characterized by a comprehensive quantitative deficiency in mitochondrial respiratory chain (MRC) complexes. The development of a reliable animal model for COXPD4 is crucial for elucidating the roles and mechanisms of TUFM in disease pathogenesis and benefiting its medical management. In this study, we construct a zebrafish tufm/ mutant that closely resembles the COXPD4 syndrome, exhibiting compromised mitochondrial protein translation, dysfunctional mitochondria with oxidative phosphorylation (OXPHOS) defects, and significant metabolic suppression of the tricarboxylic acid (TCA) cycle. Leveraging this COXPD4 zebrafish model, we comprehensively validate the clinical relevance of TUFM mutations and identify probucol as a promising therapeutic approach for managing COXPD4. Our data offer valuable insights for understanding mitochondrial diseases and developing effective treatments.

DOI: 10.1016/j.jgg.2024.05.009

Source: https://www.sciencedirect.com/science/article/abs/pii/S167385272400122X