title: Functional and regulatory profiling of energy metabolism in fission yeast.
abstract: The control of energy metabolism is fundamental for cell growth and function and anomalies in it are implicated in complex diseases and ageing. Metabolism in yeast cells can be manipulated by supplying different carbon sources: yeast grown on glucose rapidly proliferates by fermentation, analogous to tumour cells growing by aerobic glycolysis, whereas on non-fermentable carbon sources metabolism shifts towards respiration.
  
  
  
  We screened deletion libraries of fission yeast to identify over 200 genes required for respiratory growth. Growth media and auxotrophic mutants strongly influenced respiratory metabolism. Most genes uncovered in the mutant screens have not been implicated in respiration in budding yeast. We applied gene-expression profiling approaches to compare steady-state fermentative and respiratory growth and to analyse the dynamic adaptation to respiratory growth. The transcript levels of most genes functioning in energy metabolism pathways are coherently tuned, reflecting anticipated differences in metabolic flows between fermenting and respiring cells. We show that acetyl-CoA synthase, rather than citrate lyase, is essential for acetyl-CoA synthesis in fission yeast. We also investigated the transcriptional response to mitochondrial damage by genetic or chemical perturbations, defining a retrograde response that involves the concerted regulation of distinct groups of nuclear genes that may avert harm from mitochondrial malfunction.
  
  
  
  This study provides a rich framework of the genetic and regulatory basis of energy metabolism in fission yeast and beyond, and it pinpoints weaknesses of commonly used auxotroph mutants for investigating metabolism. As a model for cellular energy regulation, fission yeast provides an attractive and complementary system to budding yeast.
authors.affiliation: Research Department of Genetics, Evolution & Environment and Institute of Healthy Ageing, University College London, London, WC1E 6BT, UK.|Department of Genetics and Biotechnology, Faculty of Biology, University of Warsaw, Warsaw, Poland.
authors.forename: Michal
authors.initials: M
authors.lastname: Malecki
authors.affiliation: Research Department of Genetics, Evolution & Environment and Institute of Healthy Ageing, University College London, London, WC1E 6BT, UK.
authors.forename: Danny A
authors.initials: DA
authors.lastname: Bitton
authors.affiliation: Research Department of Genetics, Evolution & Environment and Institute of Healthy Ageing, University College London, London, WC1E 6BT, UK.
authors.forename: Maria
authors.initials: M
authors.lastname: Rodríguez-López
authors.affiliation: Research Department of Genetics, Evolution & Environment and Institute of Healthy Ageing, University College London, London, WC1E 6BT, UK.|Present address: School of Health, Sport and Biosciences, University of East London, London, E15 4LZ, UK.
authors.forename: Charalampos
authors.initials: C
authors.lastname: Rallis
authors.affiliation: Research Department of Genetics, Evolution & Environment and Institute of Healthy Ageing, University College London, London, WC1E 6BT, UK.
authors.forename: Noelia Garcia
authors.initials: NG
authors.lastname: Calavia
authors.affiliation: Research Department of Genetics, Evolution & Environment and Institute of Healthy Ageing, University College London, London, WC1E 6BT, UK.
authors.forename: Graeme C
authors.initials: GC
authors.lastname: Smith
authors.affiliation: Research Department of Genetics, Evolution & Environment and Institute of Healthy Ageing, University College London, London, WC1E 6BT, UK. j.bahler@ucl.ac.uk.
authors.forename: Jürg
authors.initials: J
authors.lastname: Bähler
mesh_terms: D000105:Acetyl Coenzyme A / Q000378:metabolism; D000220:Adaptation, Biological; D002467:Cell Nucleus / Q000235:genetics / Q000378:metabolism; D004734:Energy Metabolism / Q000235:genetics*; D005285:Fermentation; D020869:Gene Expression Profiling; D015966:Gene Expression Regulation, Fungal; D005947:Glucose / Q000378:metabolism; D059014:High-Throughput Nucleotide Sequencing; D008928:Mitochondria / Q000235:genetics / Q000378:metabolism; D009154:Mutation; D012568:Schizosaccharomyces / Q000235:genetics* / Q000378:metabolism*; D015398:Signal Transduction; D059467:Transcriptome
chemical_list: D000105:Acetyl Coenzyme A; D005947:Glucose