Insights Into the Peroxisomal Protein Inventory of Zebrafish.

Maki Kamoshita,Markus Islinger,Marco Anteghini,Vítor Martins Dos Santos,Michael Schrader,Rechal Kumar,Markus Kunze

doi:10.3389/fphys.2022.822509

Abstract

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.

Highlights

Peroxisomes represent ubiquitous, single-membrane bound subcellular compartments in eukaryotes
The zebrafish Danio rerio is developing as a promising vertebrate model to investigate peroxisome biology (Van Veldhoven and Baes, 2013), but a comprehensive analysis of the D. rerio peroxisomal protein inventory, metabolic pathways and protein targeting is lacking
For identification of proteins with a potential peroxisomal targeting signal, we screened the proteome of D. rerio5 for proteins with a PTS1 or Peroxisomal targeting signal 2 (PTS2) sequence (PTS2 based on orthologous protein sequences)

Summary

Introduction

Peroxisomes represent ubiquitous, single-membrane bound subcellular compartments in eukaryotes. They are oxidative organelles with important functions in cellular lipid metabolism and redox homeostasis (Islinger et al, 2018). Loss of functional peroxisomes or enzyme deficiencies in humans result in an accumulation of undegraded molecules. In addition to lipid metabolism, mammalian peroxisomes play a role in several non-lipid metabolic pathways such as purine, polyamine, glyoxylate, and amino acid metabolism. Due to their role in H2O2 metabolism and ROS homeostasis, peroxisomes have been linked to cellular ageing and agerelated disorders as well as cancer (Fransen et al, 2013; Islinger et al, 2018). The role of peroxisomes in the functioning of tissues and organs or during developmental processes remains largely unresolved

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Conclusion