Pablo Ranea-Robles is a postdoctoral fellow at the Mount Sinai School of Medicine in New York, where he investigates lipid metabolism inside the cell. He has been a preLighter since the beginning of 2019, and has highlighted a number of preprints covering various aspects of metabolism.
Pablo recently posted a preprint from his postdoc, so we asked him to tell us about this new research and why posting it on bioRxiv was important to him.
Deficiency of peroxisomal L-bifunctional protein (EHHADH) causes male-specific kidney hypertrophy and proximal tubular injury in mice
Pablo Ranea-Robles, Kensey Portman, Aaron Bender, Kyung Lee, John Cijiang He, David J Mulholland, Carmen Argmann, Sander M Houten
(bioRxiv, 2021) https://doi.org/10.1101/2021.03.14.435187
Could you tell us about the background and main findings of your preprint?
Peroxisomes are organelles inside the cell that perform several key physiological functions related to lipid metabolism. Lipids are used as the primary fuel source in the kidney, particularly in the proximal tubule cells which need a lot of energy to perform their function. Proximal tubule cells are also enriched in peroxisomes.
Although the role of mitochondrial fatty acid oxidation in kidney physiology is well known, the role of peroxisomes is unknown. Peroxisomal L-bifunctional protein (EHHADH) is an enzyme involved in fatty acid degradation and is highly expressed in kidney and liver of mice and humans. The function of EHHADH has remained enigmatic, as patients with a functional defect in EHHADH have not been identified yet and the Ehhadh KO mouse model has no reported major clinical phenotypic presentation.
In this study, we found that mice deficient in EHHADH spontaneously develop proximal tubule injury – but only in male mice. Our study provides a novel mouse model for sex-specific metabolic kidney injury caused by a peroxisomal dysfunction. This study also shows that peroxisomal fatty acid oxidation is a sexually dimorphic pathway in mouse kidneys. These findings may be relevant for the pathophysiology of kidney diseases, which are more prevalent in men than in women.
Figure panel 1D from the preprint showing H&E and PAS staining of kidney sections in wild-type and Ehhadh KO mice
Why did you decide to preprint your work?
Several reasons. First, posting our work as a preprint allows us to share our findings immediately with the scientific community. With this, we can get feedback on our study before it is published in the journal, and we can use these comments to improve it. Taking into account the typical procedure involved with publishing a manuscript in a journal, we are able to share these results months in advance. We can also prove what we are doing with taxpayer money that has funded the federal grants we obtained to perform this study. By sharing our research publicly, we can also show the entire research community what we are doing, and this could end in fruitful relationships and collaborations with other researchers interested in similar topics. We were also impacted by several preprints on this topic that helped us to understand our findings.