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.
Highlights
Mitochondrial membrane assembly requires the import of proteins and lipids
We describe the isolation of a new Etn auxotroph with the characteristics expected for a mutant with a defect in PtdSer transport from the MAM to the mitochondria
The new mutant, designated pstA1-1, is the first that we have discovered in the PSTA pathway, that we propose regulates aminoglycerophospholipid movement to the mitochondria
Summary
Mitochondrial membrane assembly requires the import of proteins and lipids. Whereas much is known regarding mitochondrial protein import [1, 2], little is known at the molecular level about mitochondrial import of phospholipids [3]. PtdSer is transported to the site of PtdSer decarboxylase 1 (Psd1p) in the inner mitochondrial membrane, where it is converted to phosphatidylethanolamine (PtdEtn) [5,6,7,8]. This routing of PtdSer appears true for all eukaryotes. The question of how PtdSer is transported from the ER to the inner mitochondrial membrane for PtdEtn production is an issue of major importance for cellular functions other than mitochondrial biogenesis. No protein or gene product has been identified that mediates or regulates ER to mitochondria membrane association and/or transport of PtdSer between these organelles
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