Ergosterol content specifies targeting of tail-anchored proteins to mitochondrial outer membranes

Krumpe, Katrin; Frumkin, Idan; Herzig, Yonatan; Rimon, Nitzan; Özbalci, Cagakan; Brügger, Britta; Rapaport, Doron; Schuldiner, Maya

doi:10.1091/mbc.e11-12-0994

Cited by 124 publications

(137 citation statements)

References 55 publications

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“…In the latter cases, mitochondria were usually aggregated, probably due to the elevated levels of GFP-Om14 in the MOM. However, in contrast to mutants that affect targeting of MOM single-span proteins (33,34), none of the inspected strains displayed mistargeting to other organelles. Manually annotating the resulting images for changes in localization or automatically extracting intensity data, we could find 146 strain backgrounds with altered intensity and/or altered localization of the GFP construct (see Table S1 in the supplemental material).…”

Section: Gfp-om14 Serves As a Model Protein For Correct Membrane Insementioning

confidence: 85%

Genome-Wide Screens in Saccharomyces cerevisiae Highlight a Role for Cardiolipin in Biogenesis of Mitochondrial Outer Membrane Multispan Proteins

Sauerwald

Jores

Eisenberg-Bord

et al. 2015

Molecular and Cellular Biology

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A special group of mitochondrial outer membrane (MOM) proteins spans the membrane several times via multiple helical segments. Such multispan proteins are synthesized on cytosolic ribosomes before their targeting to mitochondria and insertion into the MOM. Previous work recognized the import receptor Tom70 and the mitochondrial import (MIM) complex, both residents of the MOM, as required for optimal biogenesis of these proteins. However, their involvement is not sufficient to explain either the entire import pathway or its regulation. To identify additional factors that are involved in the biogenesis of MOM multispan proteins, we performed complementary high-throughput visual and growth screens in Saccharomyces cerevisiae. Cardiolipin (CL) synthase (Crd1) appeared as a candidate in both screens. Our results indeed demonstrate lower steady-state levels of the multispan proteins Ugo1, Scm4, and Om14 in mitochondria from crd1⌬ cells. Importantly, MOM single-span proteins were not affected by this mutation. Furthermore, organelles lacking Crd1 had a lower in vitro capacity to import newly synthesized Ugo1 and Scm4 molecules. Crd1, which is located in the mitochondrial inner membrane, condenses phosphatidylglycerol together with CDP-diacylglycerol to obtain de novo synthesized CL molecules. Hence, our findings suggest that CL is an important component in the biogenesis of MOM multispan proteins.

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Section: Gfp-om14 Serves As a Model Protein For Correct Membrane Insementioning

confidence: 85%

Genome-Wide Screens in Saccharomyces cerevisiae Highlight a Role for Cardiolipin in Biogenesis of Mitochondrial Outer Membrane Multispan Proteins

Sauerwald

Jores

Eisenberg-Bord

et al. 2015

Molecular and Cellular Biology

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“…Similarly, it has been shown that downregulation of genes involved in ergosterol biosynthesis leads to a severe mitochondrial morphology phenotype , suggesting an important role of ergosterol in overall organelle morphogenesis. Furthermore, the proper membrane integration of some single-span mitochondrial MOM proteins requires a low ergosterol content of the membrane (Kemper et al, 2008;Krumpe et al, 2012;Merklinger et al, 2012). Moreover, it is tempting to assume that the function of protein translocases and especially insertases depends on the biophysical properties of the membrane they are embedded in and therefore on the lipid composition of these membranes.…”

Section: Discussionmentioning

confidence: 99%

Mcp1 and Mcp2, two novel proteins involved in mitochondrial lipid homeostasis

Tan

Özbalci

Brügger

et al. 2013

Journal of Cell Science

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SummaryThe yeast mitochondrial outer membrane (MOM) protein Mdm10 is involved in at least three different processes: (1) association of mitochondria with the endoplasmic reticulum and mitochondrial lipid homeostasis (2) membrane assembly of MOM proteins, and (3) inheritance and morphogenesis of mitochondria. To decipher the precise role of Mdm10 in mitochondrial function, we screened for high-copy suppressors of the severe growth defect of the mdm10D mutant. We identified two novel mitochondrial proteins (open reading frames YOR228c and YLR253w) that we named Mdm10 complementing protein (Mcp) 1 and Mcp2. Overexpression of Mcp1 or Mcp2 restores the alterations in morphology and stability of respiratory chain complexes of mitochondria devoid of Mdm10, but the observed defect in assembly of MOM proteins is not rescued. Lipid analysis demonstrates that elevated levels of Mcp1 and Mcp2 restore the alterations in mitochondrial phospholipid and ergosterol homeostasis in cells lacking Mdm10. Collectively, this work identifies two novel proteins that play a role in mitochondrial lipid homeostasis and describes a role of Mdm10 in ergosterol trafficking.

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“…It remains unknown whether a protein-based machinery exists for the insertion of C-terminally anchored (tail-anchored) proteins into the outer membrane. It appears that the lipid composition of the outer membrane is a major requirement for integrating of the tail-anchored proteins (64)(65)(66). Interestingly, in the case of Tom22, the receptor and organizer of TOM that is also C-terminally anchored, a requirement for both the TOM and SAM complexes for its biogenesis has been demonstrated (67).…”

Section: Specific Transport Pathways and Their Interplays With Major mentioning

confidence: 99%

Mitochondrial protein homeostasis

2013

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Mitochondria use 800-1,500 proteins to perform their biological functions in the eukaryotic cells. Distinct transport and sorting mechanisms are responsible for the delivery of proteins to the correct location within mitochondria. Mitochondrial proteins undergo processing events and form functional assemblies.Finally, non-functional proteins are cleared to maintain healthy mitochondria. We provide an overview of the processes collectively contributing to the maintenance of mitochondrial protein homeostasis, which is critical for cell physiology and survival.

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Ergosterol content specifies targeting of tail-anchored proteins to mitochondrial outer membranes

Cited by 124 publications

References 55 publications

Genome-Wide Screens in Saccharomyces cerevisiae Highlight a Role for Cardiolipin in Biogenesis of Mitochondrial Outer Membrane Multispan Proteins

Genome-Wide Screens in Saccharomyces cerevisiae Highlight a Role for Cardiolipin in Biogenesis of Mitochondrial Outer Membrane Multispan Proteins

Mcp1 and Mcp2, two novel proteins involved in mitochondrial lipid homeostasis

Mitochondrial protein homeostasis

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