title: GLTSCR2/PICT1 links mitochondrial stress and Myc signaling.
abstract: Mitochondrial defects underlie a multitude of human diseases. Genetic manipulation of mitochondrial regulatory pathways represents a potential therapeutic approach. We have carried out a high-throughput overexpression screen for genes that affect mitochondrial abundance or activity using flow-cytometry-based enrichment of a cell population expressing a high-complexity, concentration-normalized pool of human ORFs. The screen identified 94 candidate mitochondrial regulators including the nuclear protein GLTSCR2, also known as PICT1. GLTSCR2 enhances mitochondrial function and is required for the maintenance of oxygen consumption, consistent with a pivotal role in the control of cellular respiration. RNAi inactivation of the Caenorhabditis elegans ortholog of GLTSCR2 reduces respiration in worms, indicating functional conservation across species. GLTSCR2 controls cellular proliferation and metabolism via the transcription factor Myc, and is induced by mitochondrial stress, suggesting it may constitute a significant component of the mitochondrial signaling pathway.
authors.affiliation: Department of Genetics, Harvard Medical School, Boston, MA 02115.
authors.forename: John C
authors.initials: JC
authors.lastname: Yoon
authors.forename: Alvin J Y
authors.initials: AJ
authors.lastname: Ling
authors.forename: Meltem
authors.initials: M
authors.lastname: Isik
authors.forename: Dong-Young Donna
authors.initials: DY
authors.lastname: Lee
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Steinbaugh
authors.forename: Laura M
authors.initials: LM
authors.lastname: Sack
authors.forename: Abigail N
authors.initials: AN
authors.lastname: Boduch
authors.forename: T Keith
authors.initials: TK
authors.lastname: Blackwell
authors.forename: David A
authors.initials: DA
authors.lastname: Sinclair
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Elledge
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D015153:Blotting, Western; D017173:Caenorhabditis elegans; D002478:Cells, Cultured; D017931:DNA Primers / Q000235:genetics; D030541:Databases, Genetic; D005434:Flow Cytometry; D006801:Humans; D047468:Immunoprecipitation; D046228:Microarray Analysis; D008928:Mitochondria / Q000378:metabolism / Q000502:physiology*; D016366:Open Reading Frames / Q000235:genetics; D010101:Oxygen Consumption / Q000502:physiology; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism*; D034622:RNA Interference; D015398:Signal Transduction / Q000502:physiology*; D013312:Stress, Physiological / Q000502:physiology; D025521:Tumor Suppressor Proteins / Q000378:metabolism*
chemical_list: D017931:DNA Primers; C489427:MYC protein, human; C500712:NOP53 protein, human; D016271:Proto-Oncogene Proteins c-myc; D025521:Tumor Suppressor Proteins; D000255:Adenosine Triphosphate