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DYRK1A signalling synchronizes the mitochondrial import pathways for metabolic rewiring.
Adinarayana Marada1, Corvin Walter1,2, Tamara Suhm1
1Institute of Biochemistry and Molecular Biology, ZBMZ, Faculty of Medicine, University of Freiburg, 79104, Freiburg, Germany.
Nature Communications
|June 20, 2024
Summary
DYRK1A kinase regulates mitochondrial protein import by phosphorylating TOM70. This study identifies TOM20 as a MIC19 receptor and reveals off-target effects of CK2 inhibitors on mitochondrial import pathways.
Area of Science:
- Mitochondrial biology
- Cellular signaling
- Protein import machinery
Background:
- Mitochondria require dynamic proteome adaptation for metabolic reactions.
- The TOM complex in the outer mitochondrial membrane controls protein import.
- Cytosolic kinases can modulate the TOM complex activity.
Purpose of the Study:
- To investigate the molecular details of TOM70 phosphorylation by DYRK1A.
- To clarify the roles of TOM70 and TOM20 in mitochondrial protein import.
- To assess the impact of CK2 inhibitors on mitochondrial import pathways.
Main Methods:
- Phosphorylation site analysis of TOM70.
- Investigating protein-receptor interactions for MIC19.
- Assessing the effects of CX4945 on TOM70 and TOM20 import functions.
Main Results:
- TOM70 is phosphorylated by DYRK1A at Ser91, facilitating protein transfer to the TOM complex.
- TOM70 is not a target of CK2, nor an import receptor for MIC19.
- TOM20 is identified as the MIC19 import receptor.
- The CK2 inhibitor CX4945 inhibits the DYRK1A-TOM70 pathway and activates TOM20-dependent import.
Conclusions:
- DYRK1A signaling synchronizes TOM70 and TOM20 import pathways for metabolic adaptation.
- DYRK1A acts as a cytosolic kinase regulating mitochondrial protein biogenesis.
- Off-target effects of CK2 inhibitors can modulate mitochondrial protein import.
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