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The role of mitochondrial peptide deformylase in coordinating respiratory chain assembly
Author(s) -
Battersby Brendan James,
Richter Uwe,
Lahtinen Taina,
Ruotsalainen Pilvi,
Myöhänen Maarit,
Marttinen Paula
Publication year - 2012
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.26.1_supplement.958.1
Subject(s) - mitochondrial ribosome , ribosome , methionine , mitochondrion , oxidative phosphorylation , translation (biology) , peptide , protein biosynthesis , biology , biochemistry , microbiology and biotechnology , phosphorylation , respiratory chain , cytoplasm , chemistry , amino acid , rna , gene , messenger rna
Translation of mitochondrially‐encoded proteins occurs on a dedicated set of mitochondrial ribosomes with mechanistic features more similar to their prokaryotic ancestors than that seen for cytoplasmic ribosomes. In the majority of eukaryotes, mitochondrial translation initiation requires a formyl‐methionine. In prokaryotes, the formal group and N‐terminal methionine are removed as part of the N‐terminal methionine excision (NME) pathway for protein stability. This pathway depends upon the initial deformylation reaction catalyzed by peptide deformylase. Mitochondria also contain this dedicated machinery for NME, and yet in vertebrates, only 1 of the 13 mitochondrial polypeptides has the formyl group and methionine removed from the mature protein. Loss of peptide deformylase activity leads to a defect in oxidative phosphorylation, yet the molecular basis is unknown. We have been investigating the function of Peptide deformylase in murine embryonic fibroblasts and discovered a novel regulatory loop for translation involving a retrograde response that accounts for the defect in oxidative phosphorylation, and ultimately affects the cellular growth rate. Details of this regulation will be presented.