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The mitochondrial intermembrane space–facing proteins Mcp2 and Tgl2 are involved in yeast lipid metabolism
Mitochondria are unique organelles harboring two distinct membranes, the mitochondrial inner and outer membrane (MIM and MOM, respectively). Mitochondria comprise only a subset of metabolic pathways for the synthesis of membrane lipids; therefore most lipid species and their precursors have to be im...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The American Society for Cell Biology
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6761770/ https://www.ncbi.nlm.nih.gov/pubmed/31483742 http://dx.doi.org/10.1091/mbc.E19-03-0166 |
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author | Odendall, Fenja Backes, Sandra Tatsuta, Takashi Weill, Uri Schuldiner, Maya Langer, Thomas Herrmann, Johannes M. Rapaport, Doron Dimmer, Kai Stefan |
author_facet | Odendall, Fenja Backes, Sandra Tatsuta, Takashi Weill, Uri Schuldiner, Maya Langer, Thomas Herrmann, Johannes M. Rapaport, Doron Dimmer, Kai Stefan |
author_sort | Odendall, Fenja |
collection | PubMed |
description | Mitochondria are unique organelles harboring two distinct membranes, the mitochondrial inner and outer membrane (MIM and MOM, respectively). Mitochondria comprise only a subset of metabolic pathways for the synthesis of membrane lipids; therefore most lipid species and their precursors have to be imported from other cellular compartments. One such import process is mediated by the ER mitochondria encounter structure (ERMES) complex. Both mitochondrial membranes surround the hydrophilic intermembrane space (IMS). Therefore, additional systems are required that shuttle lipids between the MIM and MOM. Recently, we identified the IMS protein Mcp2 as a high-copy suppressor for cells that lack a functional ERMES complex. To understand better how mitochondria facilitate transport and biogenesis of lipids, we searched for genetic interactions of this suppressor. We found that MCP2 has a negative genetic interaction with the gene TGL2 encoding a neutral lipid hydrolase. We show that this lipase is located in the intermembrane space of the mitochondrion and is imported via the Mia40 disulfide relay system. Furthermore, we show a positive genetic interaction of double deletion of MCP2 and PSD1, the gene encoding the enzyme that synthesizes the major amount of cellular phosphatidylethanolamine. Finally, we demonstrate that the nucleotide-binding motifs of the predicted atypical kinase Mcp2 are required for its proper function. Taken together, our data suggest that Mcp2 is involved in mitochondrial lipid metabolism and an increase of this involvement by overexpression suppresses loss of ERMES. |
format | Online Article Text |
id | pubmed-6761770 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | The American Society for Cell Biology |
record_format | MEDLINE/PubMed |
spelling | pubmed-67617702019-12-16 The mitochondrial intermembrane space–facing proteins Mcp2 and Tgl2 are involved in yeast lipid metabolism Odendall, Fenja Backes, Sandra Tatsuta, Takashi Weill, Uri Schuldiner, Maya Langer, Thomas Herrmann, Johannes M. Rapaport, Doron Dimmer, Kai Stefan Mol Biol Cell Articles Mitochondria are unique organelles harboring two distinct membranes, the mitochondrial inner and outer membrane (MIM and MOM, respectively). Mitochondria comprise only a subset of metabolic pathways for the synthesis of membrane lipids; therefore most lipid species and their precursors have to be imported from other cellular compartments. One such import process is mediated by the ER mitochondria encounter structure (ERMES) complex. Both mitochondrial membranes surround the hydrophilic intermembrane space (IMS). Therefore, additional systems are required that shuttle lipids between the MIM and MOM. Recently, we identified the IMS protein Mcp2 as a high-copy suppressor for cells that lack a functional ERMES complex. To understand better how mitochondria facilitate transport and biogenesis of lipids, we searched for genetic interactions of this suppressor. We found that MCP2 has a negative genetic interaction with the gene TGL2 encoding a neutral lipid hydrolase. We show that this lipase is located in the intermembrane space of the mitochondrion and is imported via the Mia40 disulfide relay system. Furthermore, we show a positive genetic interaction of double deletion of MCP2 and PSD1, the gene encoding the enzyme that synthesizes the major amount of cellular phosphatidylethanolamine. Finally, we demonstrate that the nucleotide-binding motifs of the predicted atypical kinase Mcp2 are required for its proper function. Taken together, our data suggest that Mcp2 is involved in mitochondrial lipid metabolism and an increase of this involvement by overexpression suppresses loss of ERMES. The American Society for Cell Biology 2019-10-01 /pmc/articles/PMC6761770/ /pubmed/31483742 http://dx.doi.org/10.1091/mbc.E19-03-0166 Text en © 2019 Odendall et al. “ASCB®,” “The American Society for Cell Biology®,” and “Molecular Biology of the Cell®” are registered trademarks of The American Society for Cell Biology. http://creativecommons.org/licenses/by-nc-sa/3.0 This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License. |
spellingShingle | Articles Odendall, Fenja Backes, Sandra Tatsuta, Takashi Weill, Uri Schuldiner, Maya Langer, Thomas Herrmann, Johannes M. Rapaport, Doron Dimmer, Kai Stefan The mitochondrial intermembrane space–facing proteins Mcp2 and Tgl2 are involved in yeast lipid metabolism |
title | The mitochondrial intermembrane space–facing proteins Mcp2 and Tgl2 are involved in yeast lipid metabolism |
title_full | The mitochondrial intermembrane space–facing proteins Mcp2 and Tgl2 are involved in yeast lipid metabolism |
title_fullStr | The mitochondrial intermembrane space–facing proteins Mcp2 and Tgl2 are involved in yeast lipid metabolism |
title_full_unstemmed | The mitochondrial intermembrane space–facing proteins Mcp2 and Tgl2 are involved in yeast lipid metabolism |
title_short | The mitochondrial intermembrane space–facing proteins Mcp2 and Tgl2 are involved in yeast lipid metabolism |
title_sort | mitochondrial intermembrane space–facing proteins mcp2 and tgl2 are involved in yeast lipid metabolism |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6761770/ https://www.ncbi.nlm.nih.gov/pubmed/31483742 http://dx.doi.org/10.1091/mbc.E19-03-0166 |
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