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 TOM70^Ser91 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 TOM70^Ser91 phosphorylation results in a strong decrease in import capacity of metabolite carriers.

SUBMITTER: Walter C 

PROVIDER: S-EPMC8277783 | biostudies-literature | 2021 Jul

REPOSITORIES: biostudies-literature