title: Genomic Analysis of ATP Efflux in Saccharomyces cerevisiae.
abstract: Adenosine triphosphate (ATP) plays an important role as a primary molecule for the transfer of chemical energy to drive biological processes. ATP also functions as an extracellular signaling molecule in a diverse array of eukaryotic taxa in a conserved process known as purinergic signaling. Given the important roles of extracellular ATP in cell signaling, we sought to comprehensively elucidate the pathways and mechanisms governing ATP efflux from eukaryotic cells. Here, we present results of a genomic analysis of ATP efflux from Saccharomyces cerevisiae by measuring extracellular ATP levels in cultures of 4609 deletion mutants. This screen revealed key cellular processes that regulate extracellular ATP levels, including mitochondrial translation and vesicle sorting in the late endosome, indicating that ATP production and transport through vesicles are required for efflux. We also observed evidence for altered ATP efflux in strains deleted for genes involved in amino acid signaling, and mitochondrial retrograde signaling. Based on these results, we propose a model in which the retrograde signaling pathway potentiates amino acid signaling to promote mitochondrial respiration. This study advances our understanding of the mechanism of ATP secretion in eukaryotes and implicates TOR complex 1 (TORC1) and nutrient signaling pathways in the regulation of ATP efflux. These results will facilitate analysis of ATP efflux mechanisms in higher eukaryotes.
authors.affiliation: The Buck Institute for Research on Aging, Novato, California 94945.
authors.forename: Theodore W
authors.initials: TW
authors.lastname: Peters
authors.affiliation: The Buck Institute for Research on Aging, Novato, California 94945.
authors.forename: Aaron W
authors.initials: AW
authors.lastname: Miller
authors.affiliation: The Buck Institute for Research on Aging, Novato, California 94945.
authors.forename: Cendrine
authors.initials: C
authors.lastname: Tourette
authors.affiliation: The Buck Institute for Research on Aging, Novato, California 94945.
authors.forename: Hannah
authors.initials: H
authors.lastname: Agren
authors.affiliation: School of Public Health, Division of Biostatistics, University of California, Berkeley, California 94729-7358.
authors.forename: Alan
authors.initials: A
authors.lastname: Hubbard
authors.affiliation: The Buck Institute for Research on Aging, Novato, California 94945 rhughes@buckinstitute.org.
authors.forename: Robert E
authors.initials: RE
authors.lastname: Hughes
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism*; D019295:Computational Biology / Q000379:methods; D056827:Endosomal Sorting Complexes Required for Transport / Q000378:metabolism; D005110:Extracellular Space / Q000378:metabolism; D063990:Gene Ontology; D016681:Genome, Fungal; D023281:Genomics / Q000379:methods; D053858:Metabolic Networks and Pathways; D008928:Mitochondria / Q000235:genetics / Q000378:metabolism; D009154:Mutation; D012441:Saccharomyces cerevisiae / Q000235:genetics* / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D056827:Endosomal Sorting Complexes Required for Transport; D000255:Adenosine Triphosphate
keywords: ATP; TORC1; mitochondria; secretion; yeast