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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...

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Autores principales: Odendall, Fenja, Backes, Sandra, Tatsuta, Takashi, Weill, Uri, Schuldiner, Maya, Langer, Thomas, Herrmann, Johannes M., Rapaport, Doron, Dimmer, Kai Stefan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The American Society for Cell Biology 2019
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.
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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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