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Phosphatidylserine Production at Membrane Contacts Sites Enhances Its Transport out of the Endoplasmic Reticulum
Author(s) -
Kannan Muthukumar,
Lahiri Sujoy,
Liu LiKa,
Prinz William A
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.660.2
Subject(s) - mitochondrion , atp synthase , endoplasmic reticulum , microbiology and biotechnology , phosphatidylethanolamine , cytoplasm , endosome , chemistry , phosphatidylserine , inner membrane , biogenesis , membrane contact site , biology , biochemistry , phospholipid , membrane , phosphatidylcholine , membrane protein , integral membrane protein , enzyme , intracellular , gene
Mitochondrial membrane biogenesis requires phospholipid import into mitochondria. One lipid that is critical for mitochondrial function, phosphatidylethanolamine (PE), is synthesized in mitochondria from phosphatidylserine (PS) that is made in the endoplasmic reticulum (ER) and imported into mitochondria. PS transfer to mitochondria occurs at regions of close contact between ER and mitochondria, often called membrane contact sites (MCSs). We investigated the mechanism of ER to mitochondria PS transport. It has long been known that PS synthase activity is enriched in portions of ER that are associated with mitochondria, called mitochondria associated membranes (MAM). We wanted to know whether the enrichment of PS synthase in MAM is necessary for efficient PS transfer to mitochondria. To address this, we generated strains in which PS synthase was located in different portions of the ER. In cells lacking endogenous PS synthase, we expressed E. coli PS synthase (PssA) in the cytoplasm or fused to Sec63p (which is all over the ER) or Mmm1p, which is enriched at ER‐mitochondrial contacts. Remarkably, only Mmm1‐PssA restores PE in mitochondria to near wild‐type levels while Sec63‐PssA or cytoplasmic PssA did not. Thus, the enrichment of PS synthase in MAM promotes PS transport to mitochondria. This finding indicates that non‐vesicular PS transport is affected by where PS is synthesized in the ER and that PS synthesized outside of MAM is not efficiently transferred to mitochondria. Interestingly, PS synthase enrichment at ER‐endosomes contacts also promote PS transport to endosomes at these junctions.