title: Spatial colocalization and functional link of purinosomes with mitochondria.
abstract: Purine biosynthetic enzymes organize into dynamic cellular bodies called purinosomes. Little is known about the spatiotemporal control of these structures. Using super-resolution microscopy, we demonstrated that purinosomes colocalized with mitochondria, and these results were supported by isolation of purinosome enzymes with mitochondria. Moreover, the number of purinosome-containing cells responded to dysregulation of mitochondrial function and metabolism. To explore the role of intracellular signaling, we performed a kinome screen using a label-free assay and found that mechanistic target of rapamycin (mTOR) influenced purinosome assembly. mTOR inhibition reduced purinosome-mitochondria colocalization and suppressed purinosome formation stimulated by mitochondria dysregulation. Collectively, our data suggest an mTOR-mediated link between purinosomes and mitochondria, and a general means by which mTOR regulates nucleotide metabolism by spatiotemporal control over protein association.
authors.affiliation: Department of Biochemistry and Cell Biology, Department of Chemistry, Stony Brook University, Stony Brook, NY 11794, USA. jarrod.french@stonybrook.edu fangy2@corning.com zhuang@chemistry.harvard.edu sjb1@psu.edu.
authors.forename: Jarrod B
authors.initials: JB
authors.lastname: French
authors.affiliation: Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA 02138, USA.
authors.forename: Sara A
authors.initials: SA
authors.lastname: Jones
authors.affiliation: Biochemical Technologies, Science and Technology Division, Corning Incorporated, Corning, NY 14831, USA.
authors.forename: Huayun
authors.initials: H
authors.lastname: Deng
authors.affiliation: Department of Chemistry, The Pennsylvania State University, University Park, PA 16802, USA.
authors.forename: Anthony M
authors.initials: AM
authors.lastname: Pedley
authors.affiliation: Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA 02138, USA. Howard Hughes Medical Institute, Harvard University, Cambridge, MA 02138, USA.
authors.forename: Doory
authors.initials: D
authors.lastname: Kim
authors.affiliation: Department of Engineering Science and Mechanics, The Pennsylvania State University, University Park, PA 16802, USA.
authors.forename: Chung Yu
authors.initials: CY
authors.lastname: Chan
authors.affiliation: Biochemical Technologies, Science and Technology Division, Corning Incorporated, Corning, NY 14831, USA.
authors.forename: Haibei
authors.initials: H
authors.lastname: Hu
authors.affiliation: Department of Chemistry, The Pennsylvania State University, University Park, PA 16802, USA.
authors.forename: Raymond J
authors.initials: RJ
authors.lastname: Pugh
authors.affiliation: Department of Chemistry, The Pennsylvania State University, University Park, PA 16802, USA.
authors.forename: Hong
authors.initials: H
authors.lastname: Zhao
authors.affiliation: Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA 02138, USA.
authors.forename: Youxin
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Engineering Science and Mechanics, The Pennsylvania State University, University Park, PA 16802, USA.
authors.forename: Tony Jun
authors.initials: TJ
authors.lastname: Huang
authors.affiliation: Biochemical Technologies, Science and Technology Division, Corning Incorporated, Corning, NY 14831, USA. jarrod.french@stonybrook.edu fangy2@corning.com zhuang@chemistry.harvard.edu sjb1@psu.edu.
authors.forename: Ye
authors.initials: Y
authors.lastname: Fang
authors.affiliation: Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA 02138, USA. Howard Hughes Medical Institute, Harvard University, Cambridge, MA 02138, USA. Department of Physics, Harvard University, Cambridge, MA 02138, USA. jarrod.french@stonybrook.edu fangy2@corning.com zhuang@chemistry.harvard.edu sjb1@psu.edu.
authors.forename: Xiaowei
authors.initials: X
authors.lastname: Zhuang
authors.affiliation: Department of Chemistry, The Pennsylvania State University, University Park, PA 16802, USA. jarrod.french@stonybrook.edu fangy2@corning.com zhuang@chemistry.harvard.edu sjb1@psu.edu.
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Benkovic
mesh_terms: D006367:HeLa Cells; D006801:Humans; D008853:Microscopy; D008928:Mitochondria / Q000378:metabolism* / Q000648:ultrastructure; D011687:Purines / Q000378:metabolism*; D015398:Signal Transduction; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*
chemical_list: D011687:Purines; D058570:TOR Serine-Threonine Kinases