Evidence That Phosphatidylserine Is Imported into Mitochondria via a Mitochondria-associated Membrane and That the Majority of Mitochondrial Phosphatidylethanolamine Is Derived from Decarboxylation of Phosphatidylserine

Abstract

Phosphatidylserine is synthesized in both the endoplasmic reticulum and a unique membrane fraction, the mitochondria-associated membrane (MAM) (Vance, 1990Vance J.E. J. Biol. Chem. 1990; 265: 7248-7256Abstract Full Text PDF PubMed Google Scholar J. Biol. Chem. 265, 7248–7256). In Chinese hamster ovary cells labeled with [3H]serine or [3H]ethanolamine, we found that the majority of mitochondrial phosphatidylethanolamine was derived from phosphatidylserine decarboxylation. Essentially no mitochondrial phosphatidylethanolamine, especially that in the inner membrane, was imported from the endoplasmic reticulum. We tested the hypothesis that phosphatidylserine made in the endoplasmic reticulum is delivered via the MAM to mitochondria for decarboxylation to phosphatidylethanolamine. Cells were pulse-labeled with [3H]serine and subsequently incubated either in the presence of hydroxylamine (for inhibition of phosphatidylserine decarboxylation) or under conditions for which cellular ATP had been depleted (for inhibition of phosphatidylserine import into mitochondria). In hydroxylamine-treated cells, within 2 h, the amount of radiolabeled phosphatidylserine in the MAM and mitochondria, but not microsomes, was greater than in untreated cells. Moreover, in ATP-depleted, but not in control, cells the amount of radiolabeled phosphatidylserine in the MAM approximately doubled by 3 h. These observations are consistent with the hypothesis that newly synthesized phosphatidylserine normally traverses the MAM en route to mitochondria. Phosphatidylserine is synthesized in both the endoplasmic reticulum and a unique membrane fraction, the mitochondria-associated membrane (MAM) (Vance, 1990Vance J.E. J. Biol. Chem. 1990; 265: 7248-7256Abstract Full Text PDF PubMed Google Scholar J. Biol. Chem. 265, 7248–7256). In Chinese hamster ovary cells labeled with [3H]serine or [3H]ethanolamine, we found that the majority of mitochondrial phosphatidylethanolamine was derived from phosphatidylserine decarboxylation. Essentially no mitochondrial phosphatidylethanolamine, especially that in the inner membrane, was imported from the endoplasmic reticulum. We tested the hypothesis that phosphatidylserine made in the endoplasmic reticulum is delivered via the MAM to mitochondria for decarboxylation to phosphatidylethanolamine. Cells were pulse-labeled with [3H]serine and subsequently incubated either in the presence of hydroxylamine (for inhibition of phosphatidylserine decarboxylation) or under conditions for which cellular ATP had been depleted (for inhibition of phosphatidylserine import into mitochondria). In hydroxylamine-treated cells, within 2 h, the amount of radiolabeled phosphatidylserine in the MAM and mitochondria, but not microsomes, was greater than in untreated cells. Moreover, in ATP-depleted, but not in control, cells the amount of radiolabeled phosphatidylserine in the MAM approximately doubled by 3 h. These observations are consistent with the hypothesis that newly synthesized phosphatidylserine normally traverses the MAM en route to mitochondria. In eukaryotes, the final stages in the biosynthesis of the majority of phospholipids occur on endoplasmic reticulum membranes (Vance and Vance, 1988Vance J.E. Biochim. Biophys. Acta. 1988; 963: 10-20Crossref PubMed Scopus (22) Google Scholar). The other membranes in the cell (e.g. mitochondria, nucleus, plasma membrane) are therefore assembled from lipids synthesized in, and exported from, the endoplasmic reticulum. An exception to this generalization is phosphatidylethanolamine which is synthesized in mitochondria by the decarboxylation of PtdSer 1The abbreviations used are: PtdSerphosphatidylserineCHOChinese hamster ovaryDMEMDulbecco’s modified Eagle’s mediumMAMmitochondria-associated membranePtdEtnphosphatidylethanolamine (Dennis and Kennedy, 1972Dennis E.A. Kennedy E.P. J. Lipid Bes. 1972; 13: 263-267Abstract Full Text PDF PubMed Google Scholar), as well as in the endoplasmic reticulum from the CDP-ethanolamine pathway (Jelsema and Morré, 1978Jelsema C.L. Morré D.J. J. Biol. Chem. 1978; 253: 7960-7971Abstract Full Text PDF PubMed Google Scholar; Vance and Vance, 1988Vance J.E. Biochim. Biophys. Acta. 1988; 963: 10-20Crossref PubMed Scopus (22) Google Scholar). An additional, minor route of PtdEtn biosynthesis is the base exchange pathway which also occurs on the endoplasmic reticulum (van Golde et al., 1974van Golde L.M.G. Raben J. Batenburg J.J. Fleischer B. Zambrano F. Fleischer S. Biochim. Biophys. Acta. 1974; 360: 179-192Crossref PubMed Scopus (116) Google Scholar; Vance and Vance, 1988Vance J.E. Biochim. Biophys. Acta. 1988; 963: 10-20Crossref PubMed Scopus (22) Google Scholar). phosphatidylserine Chinese hamster ovary Dulbecco’s modified Eagle’s medium mitochondria-associated membrane phosphatidylethanolamine Compared to other cellular membranes, mitochondrial membranes are enriched in PtdEtn. For example, in rat liver the inner and outer mitochondrial membranes contain 39 and 35%, respectively, of their total phospholipids as PtdEtn, whereas in the endoplasmic reticulum only 20% of membrane phospholipids consist of PtdEtn (Colbeau et al., 1971Colbeau A. Nachbaur J. Vignais P.M. Biochim. Biophys. Acta. 1971; 249: 462-492Crossref PubMed Scopus (497) Google Scholar. Correspondingly, in the inner and outer mitochondrial membranes the molar ratio of PtdEtn:phosphatidylcholine is 0.96 and 0.71, respectively, whereas in the endoplasmic reticulum the ratio is only 0.33. An aim of our study was to determine the biosynthetic origin of PtdEtn in mitochondrial membranes. One possibility was that all mitochondrial PtdEtn was synthesized in situ from the decarboxylation of PtdSer, which would imply that transfer of PtdEtn synthesized in the endoplasmic reticulum from CDP-ethanolamine to the mitochondria was restricted. possibility was that mitochondrial PtdEtn was derived from both CDP-ethanolamine and from PtdSer decarboxylation and that PtdEtn synthesized from the endoplasmic reticulum and mitochondria. possibility was that PtdEtn in mitochondrial membranes was synthesized in the endoplasmic reticulum from CDP-ethanolamine and that PtdEtn synthesized in mitochondria from PtdSer decarboxylation was exported to other cellular membranes. the of mitochondrial PtdEtn would to the decarboxylation of PtdSer, our of the origin of mitochondrial PtdEtn was by that PtdEtn made from PtdSer on the inner mitochondrial membrane to the outer membrane with PtdEtn in the inner mitochondrial membrane et al., F. J. Biol. Chem. 1990; 265: Full Text PDF PubMed Google Scholar; et al., B. B. B. J. Biol. Chem. Full Text PDF PubMed Google Scholar. We that in cells pulse-labeled with either or mitochondrial PtdEtn, especially that in inner membranes, was derived in situ from decarboxylation of PtdSer, was in the PtdEtn was in either inner or outer mitochondrial membranes. mitochondrial PtdEtn is derived from PtdSer and PtdSer is not synthesized in mitochondria (van Golde et al., 1974van Golde L.M.G. Raben J. Batenburg J.J. Fleischer B. Zambrano F. Fleischer S. Biochim. Biophys. Acta. 1974; 360: 179-192Crossref PubMed Scopus (116) Google Scholar; Vance and Vance, 1988Vance J.E. Biochim. Biophys. Acta. 1988; 963: 10-20Crossref PubMed Scopus (22) Google Scholar; Vance, 1990Vance J.E. J. Biol. Chem. 1990; 265: 7248-7256Abstract Full Text PDF PubMed Google we also the by which PtdSer is from of to mitochondria. of PtdSer is to occur by a that not transfer S. A. PubMed Scopus Google Scholar; Vance, J.E. J. Biol. Chem. Full Text PDF PubMed Google Scholar). that the of transfer a mitochondria of PtdSer decarboxylation) and the membranes that PtdSer J. Biol. Chem. Full Text PDF PubMed Google Scholar). The that of endoplasmic reticulum and mitochondria is by our of a mitochondria-associated membrane, the MAM (Vance, 1990Vance J.E. J. Biol. Chem. 1990; 265: 7248-7256Abstract Full Text PDF PubMed Google Scholar). The MAM was with rat liver mitochondria. the MAM of endoplasmic are the of membranes. For example, the of the endoplasmic reticulum in the MAM from rat liver is only of that in the endoplasmic reticulum. Moreover, the of biosynthetic (e.g. PtdSer and in the MAM are than in the endoplasmic reticulum (Vance, 1990Vance J.E. J. Biol. Chem. 1990; 265: 7248-7256Abstract Full Text PDF PubMed Google Scholar; et al., Vance J.E. J. Biol. Chem. Full Text PDF PubMed Google Scholar. In other biosynthetic and and phosphatidylethanolamine been in the MAM with to in the endoplasmic reticulum. In to the of the MAM in the import of newly synthesized PtdSer into mitochondria we either the decarboxylation of PtdSer or the import of PtdSer into mitochondria and of PtdSer in the hamster ovary cells were from the The and were from were from Dulbecco’s modified Eagle’s medium and medium were from and hydroxylamine were from were from were from was from The for ATP was from other were from or cells were in either in or in with of and of in was of and 3 as by under the of the cells was by the of the cells to and by the of of into the medium (Vance, J.E. J. Lipid Full Text PDF PubMed Google Scholar). with cells were with The medium was and cells were incubated with 3 of of for For cells, medium was and with of with or For cells, the the medium was with with and with or For with cells were with The cells were incubated in 3 of medium of for h. The medium was and with of with or for cells, or with with and with or for with cells. In as hydroxylamine was to the In in which was and 3 were to the medium and Vance, Vance J.E. J. Biol. Chem. Full Text PDF PubMed Google which the cellular ATP by approximately 2 h. were cells were by into and were as were from by of 3 of phospholipids were by in the of The of PtdSer and PtdEtn was from a of cells and Fleischer S. Scopus Google Scholar), and was with and cells were incubated in 3 of of for h. The medium was and cells were by and into The cells were incubated in medium with and for h. The medium was and with 3 of of for h. medium was and with medium The cells were by into and were as in were and for of For with and the was as for the with that the was with of for h, and the was for with of For the of and the of the were for and for of were on and cells were from into of from was Cells were by for and the was in of The cell was to a cell and to a of for Cells were by the cells to The in the was in of all cells as by in the mitochondria, and the MAM were from the by a to that for rat liver (Vance, 1990Vance J.E. J. Biol. Chem. 1990; 265: 7248-7256Abstract Full Text PDF PubMed Google Scholar). The was for to and cell The was for to mitochondria. The was for in a to microsomes, and the was in were as The mitochondrial was by in of medium and and the was on of of medium and in a of The was for of mitochondria, was from approximately the were with a with and by for to the The mitochondrial was in The MAM was from the as a mitochondria. The was with and for The was for in a The (MAM) was in In mitochondria were into inner and outer membranes by a to that by et al., B. B. B. J. Biol. Chem. Full Text PDF PubMed Google Scholar. The mitochondrial was in which of and 2 and mitochondrial An of in was and the was incubated for The was by of the with of a of of in The was for and mitochondrial outer and inner membranes were from the and were for the by Scopus Google Scholar), Scopus Google Scholar), and et al., B. A. J. Biol. PubMed Scopus Google Scholar. PtdSer was as that was from the (Vance and Vance, 1988Vance J.E. Biochim. Biophys. Acta. 1988; 963: 10-20Crossref PubMed Scopus (22) Google Scholar). of cells was to the of et al., J. Biol. Chem. Full Text PDF PubMed Google Scholar as a ATP were by a and J. Biol. Chem. Full Text PDF PubMed Google Scholar; and Vance, Vance J.E. J. Biol. Chem. Full Text PDF PubMed Google Scholar). and of from of the PtdSer decarboxylation and CDP-ethanolamine to mitochondrial PtdEtn were by of cells pulse-labeled with either [3H]serine or were mitochondria, microsomes, and a mitochondria-associated membrane, MAM (Vance, 1990Vance J.E. J. Biol. Chem. 1990; 265: 7248-7256Abstract Full Text PDF PubMed Google Scholar). of the membrane was by of of for endoplasmic reticulum and mitochondria and of the by mitochondria, and of mitochondria by endoplasmic were or The of the endoplasmic reticulum in the MAM was only of that in of in cell for for for for for for for in a The of the mitochondrial and in the MAM were and respectively, of in mitochondria. The presence of this of of the MAM by mitochondrial membranes was not we (Vance, 1990Vance J.E. J. Biol. Chem. 1990; 265: 7248-7256Abstract Full Text PDF PubMed Google and et al., F. F. J. Biol. Chem. Full Text PDF PubMed Google Scholar that a the MAM and mitochondria, and of mitochondria been with the The presence of mitochondrial membranes in the MAM the on the of labeled newly synthesized phospholipids for mitochondrial of the and is the ratio of the mitochondrial of of is with that of the MAM or of of the MAM mitochondrial we that than of the MAM phospholipids are the of by mitochondrial membranes. The of PtdSer which we is enriched in the MAM with the of the endoplasmic reticulum from rat liver (Vance, 1990Vance J.E. J. Biol. Chem. 1990; 265: 7248-7256Abstract Full Text PDF PubMed Google Scholar), was also In with our with rat liver (Vance, 1990Vance J.E. J. Biol. Chem. 1990; 265: 7248-7256Abstract Full Text PDF PubMed Google Scholar), the of PtdSer in the MAM from cells was approximately than that in The of PtdSer in mitochondria from cells was only of that in the that mitochondria were by of PtdSer and PtdEtn of [3H]serine into PtdSer and PtdEtn of of cells was in in the of PtdSer was in the and MAM and all the of PtdSer was in mitochondria, the of PtdSer decarboxylation. the of PtdSer was in the in PtdEtn the in of PtdSer in and the MAM the is the of exported to mitochondria for decarboxylation. the of the the of PtdEtn was in mitochondria but PtdEtn all as the These that PtdEtn in mitochondria from PtdSer decarboxylation was in mitochondria whereas was exported to other were in with cells not that the of PtdEtn was not or not the cells were of PtdEtn MAM and both the to PtdEtn from the CDP-ethanolamine both membranes contain (Vance, 1990Vance J.E. J. Biol. Chem. 1990; 265: 7248-7256Abstract Full Text PDF PubMed Google Scholar). The of PtdEtn to mitochondrial membranes was in in which cells were pulse-labeled for with [3H]ethanolamine, and the of labeled PtdEtn in was that labeled PtdEtn was in the and MAM but was not imported into mitochondria, h. Moreover, in in which the cells were incubated with for h, the of PtdEtn in mitochondria was only approximately of that in the MAM and not was for cells In both and cells, was to the medium a of in the medium the of PtdEtn by the CDP-ethanolamine and we that no of into PtdEtn would occur the of the The in of PtdEtn in the MAM and the the of labeled PtdEtn by the and of PtdEtn the of in the PtdEtn in the from of PtdSer, from in et al., F. J. Biol. Chem. 1990; 265: Full Text PDF PubMed Google Scholar and rat liver et al., B. B. B. J. Biol. Chem. Full Text PDF PubMed Google Scholar that PtdEtn synthesized from PtdSer in inner mitochondrial membranes is exported to outer mitochondrial membranes with the PtdEtn in inner membranes. We the of PtdEtn, derived from biosynthetic inner and outer mitochondrial membranes. cells were pulse-labeled with either [3H]serine or enriched in the other in membranes were from mitochondria of the outer membranes with The of the membrane was by of of for outer mitochondrial membranes and inner mitochondrial membranes of the outer membrane by inner membranes was than and of the inner membrane by outer membranes was only of in membranes of for for for for in a The of [3H]serine into PtdSer and PtdEtn in the inner and outer membranes was in in cells. in 3 the of PtdSer was in than in membranes the The PtdSer in the inner and outer membranes not h. In the of PtdEtn in the inner membranes was that in the outer membranes 3 also that the of PtdEtn in inner membranes was with that in outer membranes. of inner membranes is to the of of inner membranes by outer membranes Moreover, the amount of PtdEtn in outer membranes to of outer membranes with the the of PtdEtn in the MAM was than in mitochondrial membranes The in 3 that the CDP-ethanolamine pathway not as a of PtdEtn in inner or outer mitochondrial membranes of cells, the cells are and of for membrane The that decarboxylation of PtdSer the of mitochondrial PtdEtn. Moreover, PtdEtn is exported from mitochondria and membranes, as the MAM and endoplasmic reticulum. PtdSer for to a we the of newly made PtdSer, and PtdSer, for decarboxylation to PtdEtn. PtdSer of cells was labeled with for h, [3H]serine was for h, and was for h. in and the this in newly made PtdSer by approximately the of to PtdEtn The ratio of in as PtdSer was therefore PtdSer for decarboxylation to PtdEtn. newly made PtdSer had not been for the in PtdEtn from of and would and the ratio of in PtdEtn would These the that a of newly than PtdSer is into decarboxylation. PtdEtn was in mitochondrial membranes approximately of that in the we or not was a for of or PtdEtn to mitochondria. We therefore a the as for the in that PtdEtn was labeled with and PtdEtn was labeled for with In to the for PtdEtn, of newly made and PtdEtn were for from the endoplasmic reticulum to mitochondria the ratio of not The MAM PtdSer into that is for decarboxylation is not synthesized in mitochondria but is imported from of in the endoplasmic reticulum and the MAM (Vance, 1990Vance J.E. J. Biol. Chem. 1990; 265: 7248-7256Abstract Full Text PDF PubMed Google Scholar). The of PtdSer import into mitochondria not been of the of PtdSer in the and that the MAM and mitochondria we (Vance, 1990Vance J.E. J. Biol. Chem. 1990; 265: 7248-7256Abstract Full Text PDF PubMed Google and et al., F. F. J. Biol. Chem. Full Text PDF PubMed Google Scholar; J. Biol. Chem. Full Text PDF PubMed Google that the MAM the import of PtdSer into mitochondria. One for this hypothesis in cells was the of hydroxylamine as of PtdSer In cells this is is by hydroxylamine Biol. Full Text PDF Scopus Google Scholar; et al., J. Biol. Chem. Full Text PDF PubMed Google Scholar. the MAM were in the of PtdSer from endoplasmic reticulum to mitochondria, inhibition of PtdSer decarboxylation to of newly made PtdSer and the of decarboxylation. We therefore pulse-labeled cells with and was subsequently in medium that either or that hydroxylamine the of PtdSer to PtdEtn by approximately and a of newly synthesized PtdSer in the cells. of the cells was not by the presence of microsomes, and were from cells, and in PtdSer was We no and untreated cells in the of of the In microsomes, the of PtdSer was in cells incubated with or hydroxylamine the the amount of radiolabeled PtdSer in by approximately In the MAM from hydroxylamine-treated cells, within 2 of the of the the of PtdSer in the MAM from hydroxylamine-treated cells by approximately and the of for the of the In cells not with the In mitochondria from hydroxylamine-treated cells the in PtdSer to approximately that in mitochondria from untreated cells by and by the of the was approximately than the of the The of of the MAM from the cellular this no is for the MAM of cells. the for the MAM in rat is not in We were therefore to the of from PtdSer of with the of in PtdSer in the imply that PtdSer from [3H]serine the of the the in in the MAM and mitochondria from hydroxylamine-treated cells was the of the import of from from the endoplasmic reticulum. a for or not PtdSer made in the MAM en route to mitochondria, cells were incubated for to with and 3 which depleted the cellular ATP by approximately 2 and h. The of the cells and the of were not by the The import of PtdSer into mitochondria been to S. A. PubMed Scopus Google Scholar). of cellular ATP would to in of a to the which was The of radiolabeled PtdSer was in the microsomes, and mitochondria of that the of PtdSer to PtdEtn and in the cells. 3 the of the the amount of radiolabeled PtdSer in the MAM from cells had doubled whereas in the MAM from untreated cells the amount of the of the The amount of radiolabeled PtdSer was in mitochondria of cells than in untreated cells, import of PtdSer into mitochondria had been by ATP In microsomes, the of by the and the was the in and ATP-depleted, cells. was the for the we were to the of the MAM from the and therefore not or not the in in PtdSer in the MAM to the of from the of in the MAM from cells that the of the was imported into the MAM from membrane from endoplasmic but that the of from the MAM to mitochondria was of of In the from the with hydroxylamine and the hypothesis that the MAM is which PtdSer traverses from to mitochondria. In we we that the of PtdEtn of both inner and outer mitochondrial membranes from cells is synthesized in mitochondria from PtdSer than from the CDP-ethanolamine pathway in the endoplasmic reticulum. we that newly made PtdSer, than the of membrane PtdSer, is for decarboxylation to PtdEtn. we that PtdSer decarboxylation is by of cells with PtdSer in the MAM and mitochondria, but not in cellular ATP are PtdSer in the These for the hypothesis that the MAM the import of PtdSer into mitochondria. The in the of lipids are not is that not a of transfer Vance Vance J.E. of and Scholar). the of for of as the of and membranes in the In the we the of PtdSer, which is synthesized in the endoplasmic reticulum and membranes (Vance and Vance, 1988Vance J.E. Biochim. Biophys. Acta. 1988; 963: 10-20Crossref PubMed Scopus (22) Google Scholar), to mitochondria, PtdSer is to PtdEtn (Dennis and Kennedy, 1972Dennis E.A. Kennedy E.P. J. Lipid Bes. 1972; 13: 263-267Abstract Full Text PDF PubMed Google Scholar). of PtdSer from of to of decarboxylation on the inner mitochondrial membrane et al., J. A. PubMed Scopus Google Scholar not the of transfer was on in cells (van et al., J. Biol. Chem. 1990; 265: Full Text PDF PubMed Google cells S. A. PubMed Scopus Google Scholar; J. Biol. Chem. 1990; 265: Full Text PDF PubMed Google and of rat liver mitochondria and (Vance, J.E. J. Biol. Chem. Full Text PDF PubMed Google Scholar). The is S. A. PubMed Scopus Google and is by a which import into mitochondria J. Biol. Chem. Full Text PDF PubMed Google Scholar). These observations that of PtdSer to mitochondria occurs by a either by or in which the membranes that PtdSer into with the membranes that the decarboxylation. are with a a of from cells not the of transfer and decarboxylation of PtdSer J. Biol. Chem. 1990; 265: Full Text PDF PubMed Google Scholar). in cells that had been a which cellular but the mitochondria PtdSer only and membranes were derived from the of cells. mitochondria from of cells were used with PtdSer from a of cells, the PtdSer was not J. Biol. Chem. Full Text PDF PubMed Google Scholar). These that newly synthesized PtdSer is to mitochondria via a membrane In of the of a the membranes that and PtdSer, we a membrane fraction, the from rat liver that the of a membrane that would in the import of lipids into mitochondria (Vance, 1990Vance J.E. J. Biol. Chem. 1990; 265: 7248-7256Abstract Full Text PDF PubMed Google Scholar). is no that the MAM this observations this The MAM but not of endoplasmic but is with mitochondria The of biosynthetic in the MAM are as or in endoplasmic reticulum. In the of PtdSer is enriched in the MAM with the of endoplasmic reticulum (Vance, 1990Vance J.E. J. Biol. Chem. 1990; 265: 7248-7256Abstract Full Text PDF PubMed Google Scholar; et al., Vance J.E. J. Biol. Chem. Full Text PDF PubMed Google Scholar. for the MAM in rat phosphatidylethanolamine that is from other membranes mitochondria, plasma membrane, nucleus, and been et al., Vance J.E. Vance J. Biol. Chem. Full Text PDF PubMed Google Scholar. with rat liver for phosphatidylethanolamine that the membranes this are in in that not to the of endoplasmic reticulum but for the in the of mitochondria et al., Vance J.E. Vance J. Biol. Chem. Full Text PDF PubMed Google Scholar. the MAM to with mitochondria and we that the MAM in the of phospholipids to mitochondria. The of of membrane endoplasmic reticulum and mitochondria is not and and J. 1971; PubMed Scopus Google Scholar; and J. Biol. PubMed Scopus Google Scholar; et al., J. PubMed Scopus Google Scholar; et al., J. S. J. PubMed Scopus Google Scholar; et al., Biochim. Biophys. Acta. PubMed Scopus Google Scholar. In et al., F. F. J. Biol. Chem. Full Text PDF PubMed Google Scholar from liver a membrane that is enriched in inner and outer mitochondrial membranes. is also with endoplasmic membrane that to the MAM et al., F. F. J. Biol. Chem. Full Text PDF PubMed Google Scholar. membrane which is enriched in PtdSer and which to the MAM from cells, also been from the et al., F. J. PubMed Scopus Google Scholar. the of PtdSer One is the of the the MAM and The is on the outer of the inner mitochondrial membrane et al., J. A. PubMed Scopus Google Scholar. newly synthesized PtdSer been from biosynthetic membrane to the outer mitochondrial membrane, PtdSer is either from the inner of the outer membrane and the to the outer of the inner membrane for or the on the inner membrane to PtdSer on the inner of the outer One in which this of is via the membrane by et al., F. F. J. Biol. Chem. Full Text PDF PubMed Google Scholar in which the MAM to in with the outer mitochondrial membrane the which the outer and inner mitochondrial membranes are One that PtdSer is not the inner and outer mitochondrial membranes et al., B. B. B. J. Biol. Chem. Full Text PDF PubMed Google Scholar. are phospholipids exported from mitochondria to endoplasmic reticulum via the the of PtdEtn to the plasma membrane of occurs (Vance, 1988Vance J.E. Biochim. Biophys. Acta. 1988; 963: 10-20Crossref PubMed Scopus (22) Google Scholar), by a that is to (Vance et al., J.E. J. Biol. Chem. Full Text PDF PubMed Google Scholar. In the of PtdEtn, by to in the endoplasmic reticulum or the been in (Vance and Vance, J.E. Vance J. Biol. Chem. Full Text PDF PubMed Google Scholar; Vance, 1988Vance J.E. Biochim. Biophys. Acta. 1988; 963: 10-20Crossref PubMed Scopus (22) Google Scholar). the of transfer of lipids from mitochondria to other membranes not been We been to the of PtdEtn to the endoplasmic reticulum either in or with from rat Vance, PtdSer is to mitochondria and into PtdEtn, of PtdSer the of PtdSer, the of PtdSer was by the of PtdSer to PtdEtn was J. Biol. Chem. 1990; 265: Full Text PDF PubMed Google Scholar). that a of newly synthesized PtdSer is PtdSer for decarboxylation to PtdEtn Biochim. Biophys. Acta. PubMed Scopus Google Scholar; Vance, J.E. J. Biol. Chem. Full Text PDF PubMed Google Scholar). The of than PtdSer for decarboxylation was in the in a We also the biosynthetic origin of PtdEtn of mitochondrial membranes. In cells et al., J. Biol. Chem. Full Text PDF PubMed Google Scholar and hamster cells S. A. PubMed Scopus Google PtdSer decarboxylation is the of PtdEtn, the cells are with the of PtdEtn from In the we found that PtdEtn derived from the CDP-ethanolamine pathway not microsomes, mitochondria, and the in the presence of in the PtdEtn was imported into mitochondria. In PtdEtn of mitochondria was labeled from and the PtdEtn was also to the MAM and we that mitochondrial PtdEtn for the synthesized in situ in mitochondria via PtdSer decarboxylation. Moreover, of of PtdEtn from mitochondria the import of PtdEtn into mitochondria occurs only These with the of and Kennedy, Kennedy E.P. PubMed Scopus Google Scholar that transfer of PtdEtn from the endoplasmic reticulum to mitochondria of hamster cells with a that of and J. PubMed Scopus Google Scholar a from their in in of rat liver and mitochondria. An the origin of PtdEtn in inner mitochondrial membranes was from et al., F. J. Biol. Chem. 1990; 265: Full Text PDF PubMed Google Scholar found that newly synthesized PtdEtn in was in the outer mitochondrial membrane and not with the of PtdEtn in inner membranes. In other et al., B. B. B. J. Biol. Chem. Full Text PDF PubMed Google Scholar the decarboxylation of PtdSer in rat liver mitochondria and radiolabeled PtdSer delivered from The PtdSer was imported and to PtdEtn, but radiolabeled PtdEtn was enriched in with membranes. The of both was that PtdEtn in inner mitochondrial membranes for the not derived from newly made PtdSer but was from the CDP-ethanolamine in of was the biosynthetic origin of PtdEtn in inner mitochondrial membranes that the to mitochondrial membranes as a only of PtdEtn. In we found that the of PtdEtn derived from CDP-ethanolamine in inner membranes was only to of that in outer membranes. In the of PtdEtn in inner mitochondrial membranes was approximately that in outer membranes. we that in inner membranes the majority of PtdEtn is derived from The observations of et al., F. J. Biol. Chem. 1990; 265: Full Text PDF PubMed Google Scholar that PtdEtn of outer mitochondrial membranes was enriched in PtdEtn with that in inner membranes by of outer membranes with the of the in our the of PtdEtn derived from PtdSer in the MAM was to that in mitochondria. We no for our from of et al., B. B. B. J. Biol. Chem. Full Text PDF PubMed Google that PtdEtn was enriched in to membranes. One in our and of et al., B. B. B. J. Biol. Chem. Full Text PDF PubMed Google Scholar is that the delivered PtdSer to the outer membranes from whereas in our PtdSer was