RT Journal Article
SR Electronic
T1 Phosphatidylethanolamine made in the inner mitochondrial membrane is essential for yeast cytochrome <em>bc</em><sub>1</sub> complex function
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 269233
DO 10.1101/269233
A1 Calzada, Elizabeth
A1 McCaffery, J. Michael
A1 Claypool, Steven M.
YR 2018
UL http://biorxiv.org/content/early/2018/06/01/269233.abstract
AB 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.