TY - JOUR
T1 - Glucose-induced regulation of protein import receptor tom22 by cytosolic and mitochondria-bound kinases
AU - Gerbeth, Carolin
AU - Schmidt, Oliver
AU - Rao, Sanjana
AU - Harbauer, Angelika B.
AU - Mikropoulou, Despina
AU - Opalinska, Magdalena
AU - Guiard, Bernard
AU - Pfanner, Nikolaus
AU - Meisinger, Chris
N1 - Funding Information:
We are grateful to Dr. Jeff Kuret for yeast strains. This work was supported by the Deutsche Forschungsgemeinschaft, Excellence Initiative of the German Federal and State Governments (EXC 294 BIOSS; GSC-4 Spemann Graduate School), Bundesministerium für Bildung und Forschung (Dynamo), Sonderforschungsbereich 746, and Trinationales Graduiertenkolleg GRK 1478.
PY - 2013/10/1
Y1 - 2013/10/1
N2 - SUMMARY Most mitochondrial proteins are imported by the translocase of the outer mitochondrial membrane (TOM). Tom22 functions as central receptor and transfers preproteins to the import pore. Casein kinase 2 (CK2) constitutively phosphorylates the cytosolic precursor of Tom22 at Ser44 and Ser46 and, thus, promotes its import. It is unknown whether Tom22 is regulated under different metabolic conditions. We report that CK1, which is involved in glucose-induced signal transduction, is bound to mitochondria. CK1 phosphorylates Tom22 at Thr57 and stimulates the assembly of Tom22 and Tom20. In contrast, protein kinase A (PKA), which is also activated by the addition of glucose, phosphorylates the precursor of Tom22 at Thr76 and impairs its import. Thus, PKA functions in an opposite manner to CK1 and CK2. Our results reveal that three kinases regulate the import and assembly of Tom22, demonstrating that the central receptor is a major target for the posttranslational regulation of mitochondrial protein import.
AB - SUMMARY Most mitochondrial proteins are imported by the translocase of the outer mitochondrial membrane (TOM). Tom22 functions as central receptor and transfers preproteins to the import pore. Casein kinase 2 (CK2) constitutively phosphorylates the cytosolic precursor of Tom22 at Ser44 and Ser46 and, thus, promotes its import. It is unknown whether Tom22 is regulated under different metabolic conditions. We report that CK1, which is involved in glucose-induced signal transduction, is bound to mitochondria. CK1 phosphorylates Tom22 at Thr57 and stimulates the assembly of Tom22 and Tom20. In contrast, protein kinase A (PKA), which is also activated by the addition of glucose, phosphorylates the precursor of Tom22 at Thr76 and impairs its import. Thus, PKA functions in an opposite manner to CK1 and CK2. Our results reveal that three kinases regulate the import and assembly of Tom22, demonstrating that the central receptor is a major target for the posttranslational regulation of mitochondrial protein import.
UR - http://www.scopus.com/inward/record.url?scp=84885130330&partnerID=8YFLogxK
U2 - 10.1016/j.cmet.2013.09.006
DO - 10.1016/j.cmet.2013.09.006
M3 - Article
C2 - 24093680
AN - SCOPUS:84885130330
SN - 1550-4131
VL - 18
SP - 578
EP - 587
JO - Cell Metabolism
JF - Cell Metabolism
IS - 4
ER -