title: An Artificial Reaction Promoter Modulates Mitochondrial Functions via Chemically Promoting Protein Acetylation.
abstract: Acetylation, which modulates protein function, is an important process in intracellular signalling. In mitochondria, protein acetylation regulates a number of enzymatic activities and, therefore, modulates mitochondrial functions. Our previous report showed that tributylphosphine (PBu3), an artificial reaction promoter that promotes acetylransfer reactions in vitro, also promotes the reaction between acetyl-CoA and an exogenously introduced fluorescent probe in mitochondria. In this study, we demonstrate that PBu3 induces the acetylation of mitochondrial proteins and a decrease in acetyl-CoA concentration in PBu3-treated HeLa cells. This indicates that PBu3 can promote the acetyltransfer reaction between acetyl-CoA and mitochondrial proteins in living cells. PBu3-induced acetylation gradually reduced mitochondrial ATP concentrations in HeLa cells without changing the cytoplasmic ATP concentration, suggesting that PBu3 mainly affects mitochondrial functions. In addition, pyruvate, which is converted into acetyl-CoA in mitochondria and transiently increases ATP concentrations in the absence of PBu3, elicited a further decrease in mitochondrial ATP concentrations in the presence of PBu3. Moreover, the application and removal of PBu3 reversibly alternated mitochondrial fragmentation and elongation. These results indicate that PBu3 enhances acetyltransfer reactions in mitochondria and modulates mitochondrial functions in living cells.
authors.affiliation: Department of Biosciences and Informatics, Faculty of Science and Technology, Keio University, 3-14-1 Hiyoshi, Kohoku-ku, Yokohama, Kanagawa 223-8522, Japan.
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Shindo
authors.affiliation: MANA, National Institute for Materials Science, 1-1 Namiki, Tsukuba, Ibaraki 305-0044, Japan.
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Komatsu
authors.affiliation: Department of Biosciences and Informatics, Faculty of Science and Technology, Keio University, 3-14-1 Hiyoshi, Kohoku-ku, Yokohama, Kanagawa 223-8522, Japan.
authors.forename: Kohji
authors.initials: K
authors.lastname: Hotta
authors.affiliation: MANA, National Institute for Materials Science, 1-1 Namiki, Tsukuba, Ibaraki 305-0044, Japan.
authors.forename: Katsuhiko
authors.initials: K
authors.lastname: Ariga
authors.affiliation: Department of Biosciences and Informatics, Faculty of Science and Technology, Keio University, 3-14-1 Hiyoshi, Kohoku-ku, Yokohama, Kanagawa 223-8522, Japan.
authors.forename: Kotaro
authors.initials: K
authors.lastname: Oka
mesh_terms: D000105:Acetyl Coenzyme A / Q000737:chemistry / Q000378:metabolism; D000107:Acetylation; D000255:Adenosine Triphosphate / Q000737:chemistry / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D053938:DNA Fragmentation; D004272:DNA, Mitochondrial / Q000235:genetics*; D005456:Fluorescent Dyes; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D008928:Mitochondria / Q000378:metabolism; D024101:Mitochondrial Proteins / Q000378:metabolism*; D010720:Phosphines / Q000737:chemistry*; D019289:Pyruvic Acid / Q000378:metabolism
chemical_list: D004272:DNA, Mitochondrial; D005456:Fluorescent Dyes; D024101:Mitochondrial Proteins; D010720:Phosphines; C043255:tri-n-butylphosphine; D000105:Acetyl Coenzyme A; D019289:Pyruvic Acid; D000255:Adenosine Triphosphate