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PXD022321-1

PXD022321 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleDisturbed intramitochondrial phosphatidic acid transport impairs cellular stress signaling
DescriptionLipid transfer proteins of the Ups1/PRELID1 family facilitate the transport of phospholipids across the intermembrane space of mitochondria in a lipid-specific manner. Heterodimeric complexes of yeast Ups1/Mdm35 or human PRELID1/TRIAP1 shuttle phosphatidic acid (PA) synthesized in the endoplasmic reticulum (ER) to the inner membrane, where it is converted to cardiolipin (CL), the signature phospholipid of mitochondria. Loss of Ups1/PRELID1 proteins impairs the accumulation of CL and broadly affects mitochondrial structure and function. Unexpectedly and unlike yeast cells lacking the cardiolipin synthase Crd1, Ups1 deficient yeast cells exhibit glycolytic growth defects, pointing to functions of Ups1-mediated PA transfer beyond CL synthesis. Here, we show that the disturbed intramitochondrial transport of PA in ups1 cells leads to altered phospholipid composition of the ER membrane, independent of disturbances in CL synthesis. The impaired flux of PA into mitochondria is associated with the increased synthesis of phosphatidylcholine (PC) and a reduced phosphatidylethanolamine (PE)/PC ratio in the ER of ups1 cells which suppresses the unfolded protein response (UPR). Moreover, we observed inhibition of TORC1 signaling in these cells. Activation of either UPR by ER protein stress or of TORC1 signaling by disruption of its negative regulator, the SEACIT complex, increased cytosolic protein synthesis and restored glycolytic growth of ups1 cells. These results demonstrate that PA influx into mitochondria is required to preserve ER membrane homeostasis and that its disturbance is associated with impaired glycolytic growth and cellular stress signaling.
HostingRepositoryPRIDE
AnnounceDate2021-01-22
AnnouncementXMLSubmission_2021-01-21_23:31:31.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterHendrik Nolte
SpeciesList scientific name: Saccharomyces cerevisiae (Baker's yeast); NCBI TaxID: 4932;
ModificationListNo PTMs are included in the dataset
InstrumentQ Exactive HF
Dataset History
RevisionDatetimeStatusChangeLog Entry
02020-11-03 05:34:42ID requested
12021-01-21 23:31:32announced
Publication List
Dataset with its publication pending
Keyword List
submitter keyword: YEAST, USP1, Mitochondrion
Contact List
Thomas Langer
contact affiliationMax-Planck-Institute for Biology of Ageing Department of Mitochondrial Proteostasis Joseph-Stelzmann-Str. 9b 50931 Cologne
contact emailTLanger@age.mpg.de
lab head
Hendrik Nolte
contact affiliationMax Planck Institute for Biology of Ageing, 50931 Cologne, Germany
contact emailh.nolte@age.mpg.de
dataset submitter
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