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

Abstract

Of the four separate PE biosynthetic pathways in eukaryotes, one occurs in the mitochondrial inner membrane (IM) and is executed by phosphatidylserine decarboxylase (Psd1). Deletion of Psd1 is lethal in mice and compromises mitochondrial function. We hypothesize that this reflects inefficient import of non-mitochondrial PE into the IM. Here, we test this by re-wiring PE metabolism in yeast by re-directing Psd1 to the outer mitochondrial membrane or the endomembrane system and show that PE can cross the IMS in both directions. Nonetheless, PE synthesis in the IM is critical for cytochrome bc1 complex (III) function and mutations predicted to disrupt a conserved PE-binding site in the complex III subunit, Qcr7, impair complex III activity similar to PSD1 deletion. Collectively, these data challenge the current dogma of PE trafficking and demonstrate that PE made in the IM by Psd1 support the intrinsic functionality of complex III.

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  • Authors+Show Affiliations

    ,

    Department of Physiology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.

    ,

    Department of Physiology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.

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    Department of Physiology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.

    ,

    Department of Molecular and Cell Biology, University of Connecticut, Storrs, CT, USA.

    ,

    Barshop Institute for Longevity and Aging Studies, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA.

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    Integrated Imaging Center, Department of Biology, Johns Hopkins University, Baltimore, MD, USA.

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    Barshop Institute for Longevity and Aging Studies, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA.

    ,

    Department of Molecular and Cell Biology, University of Connecticut, Storrs, CT, USA.

    Department of Physiology, Johns Hopkins University School of Medicine, Baltimore, MD, USA. sclaypo1@jhmi.edu.

    Source

    Nature communications 10:1 2019 03 29 pg 1432

    MeSH

    Aerobiosis
    Electron Transport Complex III
    Electron Transport Complex IV
    Endoplasmic Reticulum
    Mitochondrial Membranes
    Mutation
    Phosphatidylethanolamines
    Reproducibility of Results
    Saccharomyces cerevisiae
    Saccharomyces cerevisiae Proteins

    Pub Type(s)

    Journal Article
    Research Support, N.I.H., Extramural
    Research Support, U.S. Gov't, Non-P.H.S.

    Language

    eng

    PubMed ID

    30926815

    Citation

    Calzada, Elizabeth, et al. "Phosphatidylethanolamine Made in the Inner Mitochondrial Membrane Is Essential for Yeast Cytochrome Bc1 Complex Function." Nature Communications, vol. 10, no. 1, 2019, p. 1432.
    Calzada E, Avery E, Sam PN, et al. Phosphatidylethanolamine made in the inner mitochondrial membrane is essential for yeast cytochrome bc1 complex function. Nat Commun. 2019;10(1):1432.
    Calzada, E., Avery, E., Sam, P. N., Modak, A., Wang, C., McCaffery, J. M., ... Claypool, S. M. (2019). Phosphatidylethanolamine made in the inner mitochondrial membrane is essential for yeast cytochrome bc1 complex function. Nature Communications, 10(1), p. 1432. doi:10.1038/s41467-019-09425-1.
    Calzada E, et al. Phosphatidylethanolamine Made in the Inner Mitochondrial Membrane Is Essential for Yeast Cytochrome Bc1 Complex Function. Nat Commun. 2019 03 29;10(1):1432. PubMed PMID: 30926815.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Phosphatidylethanolamine made in the inner mitochondrial membrane is essential for yeast cytochrome bc1 complex function. AU - Calzada,Elizabeth, AU - Avery,Erica, AU - Sam,Pingdewinde N, AU - Modak,Arnab, AU - Wang,Chunyan, AU - McCaffery,J Michael, AU - Han,Xianlin, AU - Alder,Nathan N, AU - Claypool,Steven M, Y1 - 2019/03/29/ PY - 2018/05/21/received PY - 2019/03/11/accepted PY - 2019/3/31/entrez PY - 2019/3/31/pubmed PY - 2019/3/31/medline SP - 1432 EP - 1432 JF - Nature communications JO - Nat Commun VL - 10 IS - 1 N2 - Of the four separate PE biosynthetic pathways in eukaryotes, one occurs in the mitochondrial inner membrane (IM) and is executed by phosphatidylserine decarboxylase (Psd1). Deletion of Psd1 is lethal in mice and compromises mitochondrial function. We hypothesize that this reflects inefficient import of non-mitochondrial PE into the IM. Here, we test this by re-wiring PE metabolism in yeast by re-directing Psd1 to the outer mitochondrial membrane or the endomembrane system and show that PE can cross the IMS in both directions. Nonetheless, PE synthesis in the IM is critical for cytochrome bc1 complex (III) function and mutations predicted to disrupt a conserved PE-binding site in the complex III subunit, Qcr7, impair complex III activity similar to PSD1 deletion. Collectively, these data challenge the current dogma of PE trafficking and demonstrate that PE made in the IM by Psd1 support the intrinsic functionality of complex III. SN - 2041-1723 UR - https://www.unboundmedicine.com/medline/citation/30926815/Phosphatidylethanolamine_made_in_the_inner_mitochondrial_membrane_is_essential_for_yeast_cytochrome_bc1_complex_function L2 - http://dx.doi.org/10.1038/s41467-019-09425-1 DB - PRIME DP - Unbound Medicine ER -