Ferredoxin 1 is essential for embryonic development and lipid homeostasis
- University of California, Davis, United States
- The University of Texas Southwestern Medical Center, United States
Abstract
Mammalian ferredoxin 1 and 2 (FDX1/2) belong to an evolutionary conserved family of iron-sulfur cluster containing proteins and act as electron shutters between ferredoxin reductase (FDXR) and numerous proteins involved in critical biological pathways. FDX1 is involved in biogenesis of steroids and bile acids, Vitamin A/D metabolism, and lipoylation of tricarboxylic acid (TCA) cycle enzymes. FDX1 has been extensively characterized biochemically but its role in physiology and lipid metabolism has not been explored. In this study, we generated Fdx1-deficient mice and showed that knockout of both alleles of the Fdx1 gene led to embryonic lethality. We also showed that like Fdxr+/- mice, Fdx1+/- mice had a shorter life span and were prone to steatohepatitis. However, unlike Fdxr+/- mice, Fdx1+/- mice were not prone to spontaneous tumors. Additionally, we showed that FDX1 deficiency led to lipid droplet accumulation possibly via the ABCA1-SREBP1/2 pathway. Specifically, untargeted lipidomic analysis showed that FDX1 deficiency led to alterations in several classes of lipids, including cholesterol, triacylglycerides, acylcarnitines, ceramides, phospholipids and lysophospholipids. Taken together, our data indicate that FDX1 is essential for mammalian embryonic development and lipid homeostasis at both cellular and organismal levels.
Data availability
The authors confirm that the data supporting the findings of this study are available within the article, its supplementary materials and source data files.
Article and author information
Author details
Funding
National Institutes of Health (CA224433)
- Xinbin Chen
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: All animal procedures were approved by UC Davis IACUC in adherence to the NIH "Guide for the Care and Use of Laboratory Animals". under the protocol # 23011.
Copyright
© 2024, Mohibi et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Ferredoxin 1 is essential for embryonic development and lipid homeostasis
eLife 13:e91656.
https://doi.org/10.7554/eLife.91656
