A work recently published in Free Radical Biology and Medicine by the group led by Dr. M. Cristina Vega at the Centro de Investigaciones Biológicas (CSIC), has revealed the atomic structure of two eukaryotic catalases from yeast species which are relevant models for peroxisomal diseases, providing insight into the roles played by peroxisomal catalases in pathogenic yeasts to resist the oxidative burst of the immune response from the human host.
Catalases are highly reactive heme-dependent enzymes that break down hydrogen peroxide (H2O2) and can be found in peroxisomes, mitochondria, cytosol and chloroplasts. By scavenging reactive oxygen species (ROS), catalases contribute to the preservation of cellular homeostasis and the prevention of cell and tissue oxidative damage. In humans, numerous diseases arise from peroxisomal malfunction, which causes ROS accumulation and cytotoxicity. Yeast peroxisomes, and their peroxisomal catalases, have been widely used as models for oxidative metabolism, ROS generation, detoxification and associated pathologies.
The work by Gómez et al. now closes a gap in knowledge about the detailed atomic structures of two eukaryotic catalases from the yeasts Komagataella phaffii (Pichia pastoris) and Kluyveromyces lactis. Both catalase structures contain NADPH as a second cofactor and are stabilized by K+ and Na+ ions. The study provides evidence that these peroxisomal catalases offer protection against conditions that are characteristic of the osmotic shock/cationic attack and the H2O2 released by neutrophils and macrophages during the oxidative burst, with implications for oxidative stress and infection biology.
These findings will increase our understanding of the sensitivity of pathogenic yeasts to the oxidative burst of innate immunity, and the molecular mechanisms deployed to counteract it.
The work was funded by AEI/FEDER (SAF2015-72961-EXP, RTI2018-102242-B-I00), Regional Government of Madrid (S2017/BMD-3673), and the CSIC (PIE 20160E064).
Reference: Peroxisomal catalases from the yeasts Pichia pastoris and Kluyveromyces lactis as models for oxidative damage in higher eukaryotes. Sara Gómez, Sergio Navas-Yuste, Asia M. Payne, Wilmaris Rivera, Miguel López-Estepa, Clotilde Brangbour, Daniel Fullà, Judith Juanhuix, Francisco J. Fernández, M. Cristina Vega (2019). Free Radical Biology and Medicine 141, 279-290. (https://doi.org/10.1016/j.freeradbiomed.2019.06.025).