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Phosphatidylethanolamine made in the inner mitochondrial membrane is essential for yeast cytochrome bc1 complex function

Elizabeth Calzada, J. Michael McCaffery, View ORCID ProfileSteven M. Claypool
doi: https://doi.org/10.1101/269233
Elizabeth Calzada
1Department of Physiology, Johns Hopkins University School of Medicine, Baltimore, MD, USA
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J. Michael McCaffery
2Integrated Imaging Center, Department of Biology, Johns Hopkins University, Baltimore, MD
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Steven M. Claypool
1Department of Physiology, Johns Hopkins University School of Medicine, Baltimore, MD, USA
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  • ORCID record for Steven M. Claypool
  • For correspondence: sclaypo1@jhmi.edu
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ABSTRACT

Of the four separate PE biosynthetic pathways in eukaryotes, one occurs in the mitochondrial inner membrane (IM) and is executed by phosphatidylserine decarboxylase (Psd1p). Deletion of Psd1, which is lethal in mice, compromises mitochondrial function. We hypothesize that this reflects inefficient import of non-mitochondrial PE into the IM. To test this, we re-wired PE metabolism in yeast by re-directing Psd1p to the outer mitochondrial membrane or the endomembrane system. Our biochemical and functional analyses identified the IMS as the greatest barrier for PE import and demonstrated that PE synthesis in the IM is critical for cytochrome bc1 complex (III) function. Importantly, mutations predicted to disrupt a conserved PE-binding site in the complex III subunit, Qcr7p, impaired complex III activity similar to PSD1 deletion. Collectively, these data demonstrate that PE made in the IM by Psd1p is critical to support the intrinsic functionality of complex III and establish one likely mechanism.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted June 01, 2018.
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Phosphatidylethanolamine made in the inner mitochondrial membrane is essential for yeast cytochrome bc1 complex function
Elizabeth Calzada, J. Michael McCaffery, Steven M. Claypool
bioRxiv 269233; doi: https://doi.org/10.1101/269233
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Phosphatidylethanolamine made in the inner mitochondrial membrane is essential for yeast cytochrome bc1 complex function
Elizabeth Calzada, J. Michael McCaffery, Steven M. Claypool
bioRxiv 269233; doi: https://doi.org/10.1101/269233

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