TY - JOUR
T1 - Phosphatidylethanolamine made in the inner mitochondrial membrane is essential for yeast cytochrome bc 1 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.
N1 - Funding Information:
We would like to thank Drs. Carla Koehler (UCLA), Cathy Clarke (UCLA), Martin Ott (Stockholm University), Susan Michaelis (Johns Hopkins University School of Medicine), and George Carman (Rutgers University) for antibodies, Drs. Ya-Wen Lu, Ouma Onguka, Seun Ogunbona, Matthew G. Baile, and Murugappan Sathappa for technical assistance, and the Mass Spectrometry Core Facility at University of Texas Health Science Center at San Antonio and the Methodist Hospital Foundation. This work was supported by the National Institutes of Health (R01GM111548 to S.M.C., R01GM111548–03S1 to P.N.S, T32GM007445 to E.C., and R01GM113092 to N.N.A.) and the National Science Foundation Graduate Research Fellowship (DGE1746891 to P.N.S.). The authors declare no competing financial interests.
Publisher Copyright:
© 2019, The Author(s).
PY - 2019/12/1
Y1 - 2019/12/1
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 bc 1 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.
AB - 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 bc 1 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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U2 - 10.1038/s41467-019-09425-1
DO - 10.1038/s41467-019-09425-1
M3 - Article
C2 - 30926815
AN - SCOPUS:85063735445
SN - 2041-1723
VL - 10
JO - Nature communications
JF - Nature communications
IS - 1
M1 - 1432
ER -