Global kinome profiling reveals DYRK1A as critical activator of the human mitochondrial import machinery

Research output: Contribution to journal › Journal article › Research › peer-review

Standard

Global kinome profiling reveals DYRK1A as critical activator of the human mitochondrial import machinery. / Walter, Corvin; Marada, Adinarayana; Suhm, Tamara; Ernsberger, Ralf; Muders, Vera; Kücükköse, Cansu; Sánchez-Martín, Pablo; Hu, Zehan; Aich, Abhishek; Loroch, Stefan; Solari, Fiorella Andrea; Poveda-Huertes, Daniel; Schwierzok, Alexandra; Pommerening, Henrike; Matic, Stanka; Brix, Jan; Sickmann, Albert; Kraft, Claudine; Dengjel, Jörn; Dennerlein, Sven; Brummer, Tilman; Vögtle, F-Nora; Meisinger, Chris.

In: Nature Communications, Vol. 12, 4284, 2021.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Walter, C, Marada, A, Suhm, T, Ernsberger, R, Muders, V, Kücükköse, C, Sánchez-Martín, P, Hu, Z, Aich, A, Loroch, S, Solari, FA, Poveda-Huertes, D, Schwierzok, A, Pommerening, H, Matic, S, Brix, J, Sickmann, A, Kraft, C, Dengjel, J, Dennerlein, S, Brummer, T, Vögtle, F-N & Meisinger, C 2021, 'Global kinome profiling reveals DYRK1A as critical activator of the human mitochondrial import machinery', Nature Communications, vol. 12, 4284. https://doi.org/10.1038/s41467-021-24426-9

APA

Walter, C., Marada, A., Suhm, T., Ernsberger, R., Muders, V., Kücükköse, C., Sánchez-Martín, P., Hu, Z., Aich, A., Loroch, S., Solari, F. A., Poveda-Huertes, D., Schwierzok, A., Pommerening, H., Matic, S., Brix, J., Sickmann, A., Kraft, C., Dengjel, J., ... Meisinger, C. (2021). Global kinome profiling reveals DYRK1A as critical activator of the human mitochondrial import machinery. Nature Communications, 12, [4284]. https://doi.org/10.1038/s41467-021-24426-9

Vancouver

Walter C, Marada A, Suhm T, Ernsberger R, Muders V, Kücükköse C et al. Global kinome profiling reveals DYRK1A as critical activator of the human mitochondrial import machinery. Nature Communications. 2021;12. 4284. https://doi.org/10.1038/s41467-021-24426-9

Author

Walter, Corvin ; Marada, Adinarayana ; Suhm, Tamara ; Ernsberger, Ralf ; Muders, Vera ; Kücükköse, Cansu ; Sánchez-Martín, Pablo ; Hu, Zehan ; Aich, Abhishek ; Loroch, Stefan ; Solari, Fiorella Andrea ; Poveda-Huertes, Daniel ; Schwierzok, Alexandra ; Pommerening, Henrike ; Matic, Stanka ; Brix, Jan ; Sickmann, Albert ; Kraft, Claudine ; Dengjel, Jörn ; Dennerlein, Sven ; Brummer, Tilman ; Vögtle, F-Nora ; Meisinger, Chris. / Global kinome profiling reveals DYRK1A as critical activator of the human mitochondrial import machinery. In: Nature Communications. 2021 ; Vol. 12.

Bibtex

@article{84ab1f50558342b9a9ff117907938fab,
title = "Global kinome profiling reveals DYRK1A as critical activator of the human mitochondrial import machinery",
abstract = "The translocase of the outer mitochondrial membrane TOM constitutes the organellar entry gate for nearly all precursor proteins synthesized on cytosolic ribosomes. Thus, TOM presents the ideal target to adjust the mitochondrial proteome upon changing cellular demands. Here, we identify that the import receptor TOM70 is targeted by the kinase DYRK1A and that this modification plays a critical role in the activation of the carrier import pathway. Phosphorylation of TOM70Ser91 by DYRK1A stimulates interaction of TOM70 with the core TOM translocase. This enables transfer of receptor-bound precursors to the translocation pore and initiates their import. Consequently, loss of TOM70Ser91 phosphorylation results in a strong decrease in import capacity of metabolite carriers. Inhibition of DYRK1A impairs mitochondrial structure and function and elicits a protective transcriptional response to maintain a functional import machinery. The DYRK1A-TOM70 axis will enable insights into disease mechanisms caused by dysfunctional DYRK1A, including autism spectrum disorder, microcephaly and Down syndrome.",
keywords = "Autism Spectrum Disorder/genetics, Cytosol/metabolism, Down Syndrome/genetics, Humans, Microcephaly/genetics, Mitochondria/genetics, Mitochondrial Membrane Transport Proteins/genetics, Mitochondrial Precursor Protein Import Complex Proteins, Phosphorylation, Protein Serine-Threonine Kinases/genetics, Protein-Tyrosine Kinases/genetics, Dyrk Kinases",
author = "Corvin Walter and Adinarayana Marada and Tamara Suhm and Ralf Ernsberger and Vera Muders and Cansu K{\"u}c{\"u}kk{\"o}se and Pablo S{\'a}nchez-Mart{\'i}n and Zehan Hu and Abhishek Aich and Stefan Loroch and Solari, {Fiorella Andrea} and Daniel Poveda-Huertes and Alexandra Schwierzok and Henrike Pommerening and Stanka Matic and Jan Brix and Albert Sickmann and Claudine Kraft and J{\"o}rn Dengjel and Sven Dennerlein and Tilman Brummer and F-Nora V{\"o}gtle and Chris Meisinger",
note = "{\textcopyright} 2021. The Author(s).",
year = "2021",
doi = "10.1038/s41467-021-24426-9",
language = "English",
volume = "12",
journal = "Nature Communications",
issn = "2041-1723",
publisher = "nature publishing group",

}

RIS

TY - JOUR

T1 - Global kinome profiling reveals DYRK1A as critical activator of the human mitochondrial import machinery

AU - Walter, Corvin

AU - Marada, Adinarayana

AU - Suhm, Tamara

AU - Ernsberger, Ralf

AU - Muders, Vera

AU - Kücükköse, Cansu

AU - Sánchez-Martín, Pablo

AU - Hu, Zehan

AU - Aich, Abhishek

AU - Loroch, Stefan

AU - Solari, Fiorella Andrea

AU - Poveda-Huertes, Daniel

AU - Schwierzok, Alexandra

AU - Pommerening, Henrike

AU - Matic, Stanka

AU - Brix, Jan

AU - Sickmann, Albert

AU - Kraft, Claudine

AU - Dengjel, Jörn

AU - Dennerlein, Sven

AU - Brummer, Tilman

AU - Vögtle, F-Nora

AU - Meisinger, Chris

N1 - © 2021. The Author(s).

PY - 2021

Y1 - 2021

N2 - The translocase of the outer mitochondrial membrane TOM constitutes the organellar entry gate for nearly all precursor proteins synthesized on cytosolic ribosomes. Thus, TOM presents the ideal target to adjust the mitochondrial proteome upon changing cellular demands. Here, we identify that the import receptor TOM70 is targeted by the kinase DYRK1A and that this modification plays a critical role in the activation of the carrier import pathway. Phosphorylation of TOM70Ser91 by DYRK1A stimulates interaction of TOM70 with the core TOM translocase. This enables transfer of receptor-bound precursors to the translocation pore and initiates their import. Consequently, loss of TOM70Ser91 phosphorylation results in a strong decrease in import capacity of metabolite carriers. Inhibition of DYRK1A impairs mitochondrial structure and function and elicits a protective transcriptional response to maintain a functional import machinery. The DYRK1A-TOM70 axis will enable insights into disease mechanisms caused by dysfunctional DYRK1A, including autism spectrum disorder, microcephaly and Down syndrome.

AB - The translocase of the outer mitochondrial membrane TOM constitutes the organellar entry gate for nearly all precursor proteins synthesized on cytosolic ribosomes. Thus, TOM presents the ideal target to adjust the mitochondrial proteome upon changing cellular demands. Here, we identify that the import receptor TOM70 is targeted by the kinase DYRK1A and that this modification plays a critical role in the activation of the carrier import pathway. Phosphorylation of TOM70Ser91 by DYRK1A stimulates interaction of TOM70 with the core TOM translocase. This enables transfer of receptor-bound precursors to the translocation pore and initiates their import. Consequently, loss of TOM70Ser91 phosphorylation results in a strong decrease in import capacity of metabolite carriers. Inhibition of DYRK1A impairs mitochondrial structure and function and elicits a protective transcriptional response to maintain a functional import machinery. The DYRK1A-TOM70 axis will enable insights into disease mechanisms caused by dysfunctional DYRK1A, including autism spectrum disorder, microcephaly and Down syndrome.

KW - Autism Spectrum Disorder/genetics

KW - Cytosol/metabolism

KW - Down Syndrome/genetics

KW - Humans

KW - Microcephaly/genetics

KW - Mitochondria/genetics

KW - Mitochondrial Membrane Transport Proteins/genetics

KW - Mitochondrial Precursor Protein Import Complex Proteins

KW - Phosphorylation

KW - Protein Serine-Threonine Kinases/genetics

KW - Protein-Tyrosine Kinases/genetics

KW - Dyrk Kinases

U2 - 10.1038/s41467-021-24426-9

DO - 10.1038/s41467-021-24426-9

M3 - Journal article

C2 - 34257281

VL - 12

JO - Nature Communications

JF - Nature Communications

SN - 2041-1723

M1 - 4284

ER -

ID: 391634122