title: Mitochondrial Mg(2+) homeostasis decides cellular energy metabolism and vulnerability to stress.
abstract: Cellular energy production processes are composed of many Mg(2+) dependent enzymatic reactions. In fact, dysregulation of Mg(2+) homeostasis is involved in various cellular malfunctions and diseases. Recently, mitochondria, energy-producing organelles, have been known as major intracellular Mg(2+) stores. Several biological stimuli alter mitochondrial Mg(2+) concentration by intracellular redistribution. However, in living cells, whether mitochondrial Mg(2+) alteration affect cellular energy metabolism remains unclear. Mg(2+) transporter of mitochondrial inner membrane MRS2 is an essential component of mitochondrial Mg(2+) uptake system. Here, we comprehensively analyzed intracellular Mg(2+) levels and energy metabolism in Mrs2 knockdown (KD) cells using fluorescence imaging and metabolome analysis. Dysregulation of mitochondrial Mg(2+) homeostasis disrupted ATP production via shift of mitochondrial energy metabolism and morphology. Moreover, Mrs2 KD sensitized cellular tolerance against cellular stress. These results indicate regulation of mitochondrial Mg(2+) via MRS2 critically decides cellular energy status and cell vulnerability via regulation of mitochondrial Mg(2+) level in response to physiological stimuli.
authors.affiliation: Center for Biosciences and Informatics, School of Fundamental Science and Technology Graduate School of Science and Technology, Keio University, Yokohama, 223-8522, Kanagawa, Japan.
authors.forename: Ryu
authors.initials: R
authors.lastname: Yamanaka
authors.affiliation: Institute for Advanced Biosciences, Keio University, Kakuganji, Tsuruoka, Yamagata, 997-0052, Japan.
authors.forename: Sho
authors.initials: S
authors.lastname: Tabata
authors.affiliation: Center for Biosciences and Informatics, School of Fundamental Science and Technology Graduate School of Science and Technology, Keio University, Yokohama, 223-8522, Kanagawa, Japan.
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Shindo
authors.affiliation: Center for Biosciences and Informatics, School of Fundamental Science and Technology Graduate School of Science and Technology, Keio University, Yokohama, 223-8522, Kanagawa, Japan.
authors.forename: Kohji
authors.initials: K
authors.lastname: Hotta
authors.affiliation: Center for Science and Technology for Designing Functions, School of Integrated Design Engineering, Graduate School of Science and Technology, Keio University, Yokohama, Kanagawa, 223-8522, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Suzuki
authors.affiliation: Institute for Advanced Biosciences, Keio University, Kakuganji, Tsuruoka, Yamagata, 997-0052, Japan.
authors.forename: Tomoyoshi
authors.initials: T
authors.lastname: Soga
authors.affiliation: Center for Biosciences and Informatics, School of Fundamental Science and Technology Graduate School of Science and Technology, Keio University, Yokohama, 223-8522, Kanagawa, Japan.
authors.forename: Kotaro
authors.initials: K
authors.lastname: Oka
mesh_terms: D001692:Biological Transport / Q000235:genetics; D027682:Cation Transport Proteins / Q000235:genetics*; D045744:Cell Line, Tumor; D002468:Cell Physiological Phenomena; D004734:Energy Metabolism / Q000502:physiology*; D006367:HeLa Cells; D006706:Homeostasis / Q000502:physiology; D006801:Humans; D008274:Magnesium / Q000378:metabolism*; D053078:Membrane Potential, Mitochondrial / Q000235:genetics; D008928:Mitochondria / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000235:genetics*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics; D013312:Stress, Physiological / Q000235:genetics*
chemical_list: D027682:Cation Transport Proteins; C430096:MRS2 protein, human; D024101:Mitochondrial Proteins; D034741:RNA, Small Interfering; D008274:Magnesium