1. Cancer Biology

Ferredoxin 1 is essential for embryonic development and lipid homeostasis

  1. Shakur Mohibi
  2. Yanhong Zhang
  3. Vivian Perng
  4. Mingyi Chen
  5. Jin Zhang  Is a corresponding author
  6. Xinbin Chen  Is a corresponding author
  1. University of California, Davis, United States
  2. The University of Texas Southwestern Medical Center, United States
https://doi.org/10.7554/eLife.91656
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  1. Shakur Mohibi
  2. Yanhong Zhang
  3. Vivian Perng
  4. Mingyi Chen
  5. Jin Zhang
  6. Xinbin Chen
(2024)
Ferredoxin 1 is essential for embryonic development and lipid homeostasis
eLife 13:e91656.
https://doi.org/10.7554/eLife.91656
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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

  1. Shakur Mohibi

    Comparative Oncology Laboratory, University of California, Davis, Davis, United States
    Competing interests
    The authors declare that no competing interests exist.

  2. Yanhong Zhang

    Comparative Oncology Laboratory, University of California, Davis, Davis, United States
    Competing interests
    The authors declare that no competing interests exist.

  3. Vivian Perng

    Comparative Oncology Laboratory, University of California, Davis, Davis, United States
    Competing interests
    The authors declare that no competing interests exist.

  4. Mingyi Chen

    Department of Pathology, The University of Texas Southwestern Medical Center, Dallas, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-6754-0480

  5. Jin Zhang

    Center for Comparative Oncology, University of California, Davis, Davis, United States
    For correspondence
    jinzhang@ucdavis.edu
    Competing interests
    The authors declare that no competing interests exist.

  6. Xinbin Chen

    Comparative Oncology Laboratory, University of California, Davis, Davis, United States
    For correspondence
    xbchen@ucdavis.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-4582-6506

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.

Reviewing Editor

  1. Matthew A Quinn, Wake Forest Baptist Medical Center, United States

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.

Version history

  1. Received: August 6, 2023
  2. Preprint posted: August 24, 2023 (view preprint)
  3. Accepted: January 19, 2024
  4. Accepted Manuscript published: January 22, 2024 (version 1)
  5. Version of Record published: February 6, 2024 (version 2)

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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  1. Shakur Mohibi
  2. Yanhong Zhang
  3. Vivian Perng
  4. Mingyi Chen
  5. Jin Zhang
  6. Xinbin Chen
(2024)
Ferredoxin 1 is essential for embryonic development and lipid homeostasis
eLife 13:e91656.
https://doi.org/10.7554/eLife.91656

Share this article

https://doi.org/10.7554/eLife.91656

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