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Disease-Linked Glutarylation Impairs Function and Interactions of Mitochondrial Proteins and Contributes to Mitochondrial Heterogeneity

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Disease-Linked Glutarylation Impairs Function and Interactions of Mitochondrial Proteins and Contributes to Mitochondrial Heterogeneity. / Schmiesing, Jessica; Storch, Stephan; Dörfler, Ann-Cathrin; Schweizer, Michaela; Makrypidi-Fraune, Georgia; Thelen, Melanie; Sylvester, Marc; Gieselmann, Volkmar; Meyer-Schwesinger, Catherine; Koch-Nolte, Friedrich; Tidow, Henning; Mühlhausen, Chris; Waheed, Abdul; Sly, William S; Braulke, Thomas.

in: CELL REP, Jahrgang 24, Nr. 11, 11.09.2018, S. 2946-2956.

Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung

Harvard

Schmiesing, J, Storch, S, Dörfler, A-C, Schweizer, M, Makrypidi-Fraune, G, Thelen, M, Sylvester, M, Gieselmann, V, Meyer-Schwesinger, C, Koch-Nolte, F, Tidow, H, Mühlhausen, C, Waheed, A, Sly, WS & Braulke, T 2018, 'Disease-Linked Glutarylation Impairs Function and Interactions of Mitochondrial Proteins and Contributes to Mitochondrial Heterogeneity', CELL REP, Jg. 24, Nr. 11, S. 2946-2956. https://doi.org/10.1016/j.celrep.2018.08.014

APA

Schmiesing, J., Storch, S., Dörfler, A-C., Schweizer, M., Makrypidi-Fraune, G., Thelen, M., Sylvester, M., Gieselmann, V., Meyer-Schwesinger, C., Koch-Nolte, F., Tidow, H., Mühlhausen, C., Waheed, A., Sly, W. S., & Braulke, T. (2018). Disease-Linked Glutarylation Impairs Function and Interactions of Mitochondrial Proteins and Contributes to Mitochondrial Heterogeneity. CELL REP, 24(11), 2946-2956. https://doi.org/10.1016/j.celrep.2018.08.014

Vancouver

Schmiesing J, Storch S, Dörfler A-C, Schweizer M, Makrypidi-Fraune G, Thelen M et al. Disease-Linked Glutarylation Impairs Function and Interactions of Mitochondrial Proteins and Contributes to Mitochondrial Heterogeneity. CELL REP. 2018 Sep 11;24(11):2946-2956. https://doi.org/10.1016/j.celrep.2018.08.014

Bibtex

@article{0615b591a65a439288cae1d0f8762d7a,
title = "Disease-Linked Glutarylation Impairs Function and Interactions of Mitochondrial Proteins and Contributes to Mitochondrial Heterogeneity",
abstract = "Lysine glutarylation (Kglu) of mitochondrial proteins is associated with glutaryl-CoA dehydrogenase (GCDH) deficiency, which impairs lysine/tryptophan degradation and causes destruction of striatal neurons during catabolic crisis with subsequent movement disability. By investigating the role of Kglu modifications in this disease, we compared the brain and liver glutarylomes of Gcdh-deficient mice. In the brain, we identified 73 Kglu sites on 37 mitochondrial proteins involved in various metabolic degradation pathways. Ultrastructural immunogold studies indicated that glutarylated proteins are heterogeneously distributed in mitochondria, which are exclusively localized in glial cells. In liver cells, all mitochondria contain Kglu-modified proteins. Glutarylation reduces the catalytic activities of the most abundant glutamate dehydrogenase (GDH) and the brain-specific carbonic anhydrase 5b and interferes with GDH-protein interactions. We propose that Kglu contributes to the functional heterogeneity of mitochondria and may metabolically adapt glial cells to the activity and metabolic demands of neighboring GCDH-deficient neurons.",
keywords = "Journal Article",
author = "Jessica Schmiesing and Stephan Storch and Ann-Cathrin D{\"o}rfler and Michaela Schweizer and Georgia Makrypidi-Fraune and Melanie Thelen and Marc Sylvester and Volkmar Gieselmann and Catherine Meyer-Schwesinger and Friedrich Koch-Nolte and Henning Tidow and Chris M{\"u}hlhausen and Abdul Waheed and Sly, {William S} and Thomas Braulke",
note = "Copyright {\textcopyright} 2018 The Author(s). Published by Elsevier Inc. All rights reserved.",
year = "2018",
month = sep,
day = "11",
doi = "10.1016/j.celrep.2018.08.014",
language = "English",
volume = "24",
pages = "2946--2956",
journal = "CELL REP",
issn = "2211-1247",
publisher = "Elsevier",
number = "11",

}

RIS

TY - JOUR

T1 - Disease-Linked Glutarylation Impairs Function and Interactions of Mitochondrial Proteins and Contributes to Mitochondrial Heterogeneity

AU - Schmiesing, Jessica

AU - Storch, Stephan

AU - Dörfler, Ann-Cathrin

AU - Schweizer, Michaela

AU - Makrypidi-Fraune, Georgia

AU - Thelen, Melanie

AU - Sylvester, Marc

AU - Gieselmann, Volkmar

AU - Meyer-Schwesinger, Catherine

AU - Koch-Nolte, Friedrich

AU - Tidow, Henning

AU - Mühlhausen, Chris

AU - Waheed, Abdul

AU - Sly, William S

AU - Braulke, Thomas

N1 - Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

PY - 2018/9/11

Y1 - 2018/9/11

N2 - Lysine glutarylation (Kglu) of mitochondrial proteins is associated with glutaryl-CoA dehydrogenase (GCDH) deficiency, which impairs lysine/tryptophan degradation and causes destruction of striatal neurons during catabolic crisis with subsequent movement disability. By investigating the role of Kglu modifications in this disease, we compared the brain and liver glutarylomes of Gcdh-deficient mice. In the brain, we identified 73 Kglu sites on 37 mitochondrial proteins involved in various metabolic degradation pathways. Ultrastructural immunogold studies indicated that glutarylated proteins are heterogeneously distributed in mitochondria, which are exclusively localized in glial cells. In liver cells, all mitochondria contain Kglu-modified proteins. Glutarylation reduces the catalytic activities of the most abundant glutamate dehydrogenase (GDH) and the brain-specific carbonic anhydrase 5b and interferes with GDH-protein interactions. We propose that Kglu contributes to the functional heterogeneity of mitochondria and may metabolically adapt glial cells to the activity and metabolic demands of neighboring GCDH-deficient neurons.

AB - Lysine glutarylation (Kglu) of mitochondrial proteins is associated with glutaryl-CoA dehydrogenase (GCDH) deficiency, which impairs lysine/tryptophan degradation and causes destruction of striatal neurons during catabolic crisis with subsequent movement disability. By investigating the role of Kglu modifications in this disease, we compared the brain and liver glutarylomes of Gcdh-deficient mice. In the brain, we identified 73 Kglu sites on 37 mitochondrial proteins involved in various metabolic degradation pathways. Ultrastructural immunogold studies indicated that glutarylated proteins are heterogeneously distributed in mitochondria, which are exclusively localized in glial cells. In liver cells, all mitochondria contain Kglu-modified proteins. Glutarylation reduces the catalytic activities of the most abundant glutamate dehydrogenase (GDH) and the brain-specific carbonic anhydrase 5b and interferes with GDH-protein interactions. We propose that Kglu contributes to the functional heterogeneity of mitochondria and may metabolically adapt glial cells to the activity and metabolic demands of neighboring GCDH-deficient neurons.

KW - Journal Article

U2 - 10.1016/j.celrep.2018.08.014

DO - 10.1016/j.celrep.2018.08.014

M3 - SCORING: Journal article

C2 - 30208319

VL - 24

SP - 2946

EP - 2956

JO - CELL REP

JF - CELL REP

SN - 2211-1247

IS - 11

ER -