title: Ribonucleoprotein Y-box-binding protein-1 regulates mitochondrial oxidative phosphorylation (OXPHOS) protein expression after serum stimulation through binding to OXPHOS mRNA.
abstract: Mitochondria play key roles in essential cellular functions, such as energy production, metabolic pathways and aging. Growth factor-mediated expression of the mitochondrial OXPHOS (oxidative phosphorylation) complex proteins has been proposed to play a fundamental role in metabolic homoeostasis. Although protein translation is affected by general RNA-binding proteins, very little is known about the mechanism involved in mitochondrial OXPHOS protein translation. In the present study, serum stimulation induced nuclear-encoded OXPHOS protein expression, such as NDUFA9 [NADH dehydrogenase (ubiquinone) 1α subcomplex, 9, 39 kDa], NDUFB8 [NADH dehydrogenase (ubiquinone) 1β subcomplex, 8, 19 kDa], SDHB [succinate dehydrogenase complex, subunit B, iron sulfur (Ip)] and UQCRFS1 (ubiquinol-cytochrome c reductase, Rieske iron-sulfur polypeptide 1), and mitochondrial ATP production, in a translation-dependent manner. We also observed that the major ribonucleoprotein YB-1 (Y-box-binding protein-1) preferentially bound to these OXPHOS mRNAs and regulated the recruitment of mRNAs from inactive mRNPs (messenger ribonucleoprotein particles) to active polysomes. YB-1 depletion led to up-regulation of mitochondrial function through induction of OXPHOS protein translation from inactive mRNP release. In contrast, YB-1 overexpression suppressed the translation of these OXPHOS mRNAs through reduced polysome formation, suggesting that YB-1 regulated the translation of mitochondrial OXPHOS mRNAs through mRNA binding. Taken together, our findings suggest that YB-1 is a critical factor for translation that may control OXPHOS activity.
authors.affiliation: Department of Clinical Chemistry and Laboratory Medicine, Graduate School of Medical Sciences, Kyushu University, Higashi-ku, Fukuoka, Japan.
authors.forename: Shinya
authors.initials: S
authors.lastname: Matsumoto
authors.forename: Takeshi
authors.initials: T
authors.lastname: Uchiumi
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Tanamachi
authors.forename: Toshiro
authors.initials: T
authors.lastname: Saito
authors.forename: Mikako
authors.initials: M
authors.lastname: Yagi
authors.forename: Shinya
authors.initials: S
authors.lastname: Takazaki
authors.forename: Tomotake
authors.initials: T
authors.lastname: Kanki
authors.forename: Dongchon
authors.initials: D
authors.lastname: Kang
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D008928:Mitochondria / Q000378:metabolism*; D010084:Oxidation-Reduction; D010750:Phosphoproteins / Q000378:metabolism*; D011485:Protein Binding; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000235:genetics; D012261:Ribonucleoproteins / Q000378:metabolism*; D044967:Serum / Q000737:chemistry*; D015854:Up-Regulation; D051840:Y-Box-Binding Protein 1 / Q000378:metabolism*
chemical_list: D010750:Phosphoproteins; D012333:RNA, Messenger; D012261:Ribonucleoproteins; D051840:Y-Box-Binding Protein 1; D000255:Adenosine Triphosphate