Table_1_Insights Into the Peroxisomal Protein Inventory of Zebrafish.docx

Peroxisomes are ubiquitous, oxidative subcellular organelles with important functions in cellular lipid metabolism and redox homeostasis. Loss of peroxisomal functions causes severe disorders with developmental and neurological abnormalities. Zebrafish are emerging as an attractive vertebrate model to study peroxisomal disorders as well as cellular lipid metabolism. Here, we combined bioinformatics analyses with molecular cell biology and reveal the first comprehensive inventory of Danio rerio peroxisomal proteins, which we systematically compared with those of human peroxisomes. Through bioinformatics analysis of all PTS1-carrying proteins, we demonstrate that D. rerio lacks two well-known mammalian peroxisomal proteins (BAAT and ZADH2/PTGR3), but possesses a putative peroxisomal malate synthase (Mlsl) and verified differences in the presence of purine degrading enzymes. Furthermore, we revealed novel candidate peroxisomal proteins in D. rerio, whose function and localisation is discussed. Our findings confirm the suitability of zebrafish as a vertebrate model for peroxisome research and open possibilities for the study of novel peroxisomal candidate proteins in zebrafish and humans.

过氧化物酶体（Peroxisomes）是一类普遍存在的氧化型亚细胞器，在细胞脂质代谢与氧化还原稳态中发挥关键功能。过氧化物酶体功能缺失会引发伴随发育异常与神经功能障碍的严重疾病。斑马鱼正逐渐成为研究过氧化物酶体疾病与细胞脂质代谢的极具吸引力的脊椎动物模型。本研究结合生物信息学分析与分子细胞生物学实验，首次构建了斑马鱼（Danio rerio）过氧化物酶体蛋白的完整名录，并将其与人类过氧化物酶体蛋白进行了系统比对。通过对所有携带过氧化物酶体靶向信号1（peroxisomal targeting signal 1, PTS1）的蛋白进行生物信息学分析，本研究证实斑马鱼缺失两种经典的哺乳动物过氧化物酶体蛋白（BAAT与ZADH2/PTGR3），但拥有一种潜在的过氧化物酶体苹果酸合酶（Mlsl），并验证了嘌呤降解酶谱的存在差异。此外，本研究还发现了斑马鱼中全新的候选过氧化物酶体蛋白，并对其功能与亚细胞定位进行了探讨。本研究结果证实了斑马鱼作为过氧化物酶体研究脊椎动物模型的适用性，同时为在斑马鱼与人类中开展新型过氧化物酶体候选蛋白的研究提供了新思路。