title: Phosphatidylserine transport to the mitochondria is regulated by ubiquitination.
abstract: Mitochondrial membrane biogenesis requires the interorganelle transport of phospholipids. Phosphatidylserine (PtdSer) synthesized in the endoplasmic reticulum and related membranes (mitochondria-associated membrane (MAM)) is transported to the mitochondria by unknown gene products and decarboxylated to form phosphatidylethanolamine at the inner membrane by PtdSer decarboxylase 1 (Psd1p). We have designed a screen for strains defective in PtdSer transport (pstA mutants) between the endoplasmic reticulum and Psd1p that relies on isolating ethanolamine auxotrophs in suitable (psd2Delta) genetic backgrounds. Following chemical mutagenesis, we isolated an ethanolamine auxotroph that we designate pstA1-1. Using in vivo and in vitro phospholipid synthesis/transport measurements, we demonstrate that the pstA1-1 mutant is defective in PtdSer transport between the MAM and mitochondria. The gene that complements the growth defect and PtdSer transport defect of the pstA1-1 mutant is MET30, which encodes a substrate recognition subunit of the SCF (suppressor of kinetochore protein 1, cullin, F-box) ubiquitin ligase complex. Reconstitution of different permutations of MAM and mitochondria from wild type and pstA1-1 strains demonstrates that the MET30 gene product affects both organelles. These data provide compelling evidence that interorganelle PtdSer traffic is regulated by ubiquitination.
authors.affiliation: Department of Medicine, Program in Cell Biology, National Jewish Medical and Research Center, Denver, Colorado 80206, USA.
authors.forename: Marc M
authors.initials: MM
authors.lastname: Schumacher
authors.forename: Jae-Yeon
authors.initials: JY
authors.lastname: Choi
authors.forename: Dennis R
authors.initials: DR
authors.lastname: Voelker
mesh_terms: D001692:Biological Transport; D002794:Choline / Q000378:metabolism; D007425:Intracellular Membranes / Q000378:metabolism; D007700:Kinetics; D008928:Mitochondria / Q000378:metabolism*; D010718:Phosphatidylserines / Q000378:metabolism*; D010743:Phospholipids / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000254:growth & development / Q000502:physiology*; D025801:Ubiquitin / Q000378:metabolism*
chemical_list: D010718:Phosphatidylserines; D010743:Phospholipids; D025801:Ubiquitin; D002794:Choline