Jiang Chenxing S, Schrader Michael
Biosciences, Faculty of Health and Life Sciences, University of Exeter, Exeter EX4 4QD, UK.
Cells. 2025 Jan 20;14(2):147. doi: 10.3390/cells14020147.
Peroxisomes are ubiquitous, dynamic, oxidative organelles with key functions in cellular lipid metabolism and redox homeostasis. They have been linked to healthy ageing, neurodegeneration, cancer, the combat of pathogens and viruses, and infection and immune responses. Their biogenesis relies on several peroxins (encoded by genes), which mediate matrix protein import, membrane assembly, and peroxisome multiplication. Defects in peroxins or peroxisomal enzymes can result in severe disorders, including developmental and neurological abnormalities. The drive to understand the role of peroxisomes in human health and disease, as well as their functions in tissues and organs or during development, has led to the establishment of vertebrate models. The zebrafish () has become an attractive vertebrate model organism to investigate peroxisomal functions. Here, we provide an overview of the visualisation of peroxisomes in zebrafish, as well as the peroxisomal metabolic functions and peroxisomal protein inventory in comparison to human peroxisomes. We then present zebrafish models which have been established to investigate peroxisomal disorders. These include model zebrafish for peroxisome biogenesis disorders/Zellweger Spectrum disorders, and single enzyme deficiencies, particularly adrenoleukodystrophy and fatty acid beta-oxidation abnormalities. Finally, we highlight zebrafish models for deficiencies of dually targeted peroxisomal/mitochondrial proteins. Advantages for the investigation of peroxisomes during development and approaches to the application of zebrafish models for drug screening are discussed.
过氧化物酶体是普遍存在的、动态的氧化细胞器，在细胞脂质代谢和氧化还原稳态中发挥关键作用。它们与健康衰老、神经退行性变、癌症、病原体和病毒的对抗以及感染和免疫反应有关。其生物发生依赖于几种过氧化物酶（由基因编码），这些酶介导基质蛋白导入、膜组装和过氧化物酶体增殖。过氧化物酶或过氧化物酶体酶的缺陷可导致严重疾病，包括发育和神经异常。对过氧化物酶体在人类健康和疾病中的作用及其在组织、器官或发育过程中的功能的研究推动了脊椎动物模型的建立。斑马鱼已成为研究过氧化物酶体功能的有吸引力的脊椎动物模式生物。在这里，我们概述了斑马鱼中过氧化物酶体的可视化，以及与人类过氧化物酶体相比的过氧化物酶体代谢功能和过氧化物酶体蛋白清单。然后，我们介绍了为研究过氧化物酶体疾病而建立的斑马鱼模型。这些模型包括过氧化物酶体生物发生障碍/泽尔韦格谱系障碍的斑马鱼模型，以及单一酶缺陷模型，特别是肾上腺脑白质营养不良和脂肪酸β氧化异常模型。最后，我们重点介绍了双靶向过氧化物酶体/线粒体蛋白缺陷的斑马鱼模型。讨论了在发育过程中研究过氧化物酶体的优势以及斑马鱼模型在药物筛选中的应用方法。
