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cAMP‐dependent protein kinase promotes mitochondrial import of the nuclear encoded NDUFS4 subunit of complex I
Author(s) -
Papa Sergio,
De Rasmo Domenico,
Panelli Damiano,
Sardanelli Anna Maria
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.5.a661-c
Subject(s) - protein subunit , protein kinase a , phosphorylation , mitochondrion , autophagy related protein 13 , biochemistry , microbiology and biotechnology , oxidative phosphorylation , protein phosphorylation , biology , chemistry , gene
Most of the subunits of oxidative phosphorylation enzymes are encoded by nuclear genes, synthesized in the cytosol and imported in mitochondria. We have studied the impact of c‐AMP dependent ‐ protein kinase (PKA) on mitochondrial import of two nuclear encoded subunits of complex I. These subunits, human genes NDUFS4 (AQDQ, 18kDa protein) and NDUFB11 (ESSS protein), contain phosphorylation sites for PKA in the presequence. The first contains also a phosphorylation site in the carboxy‐terminal region. The subunits synthesized in vitro were offered to isolated mitochondria. The mitochondrial import and maturation of [ 35 S]Met labelled NDUFS4 subunit was promoted by the catalytic subunit of PKA and depressed by alkaline phosphatase (AP). The effects of PKA and AP were prevented by their respective inhibitors. PKA and AP had no effect on the import of the ESSS protein. S38A and/or S173A mutations in the phosphorylation sites of the presequence and carboxy‐terminal region respectively, abolished the import of the NDUFS4 protein. Phosphorylation of both the presequence and the carboxy‐terminal sites of the NDUFS4 protein is essential for its mitochondrial import. c‐AMP dependent protein phosphorylation appears to have a more general role in cellular protein traffic, in that it promotes the import of other mitochondrial proteins. Supported by MIUR grant n° 2005052128.