title: Dysfunctional mitochondria modulate cAMP-PKA signaling and filamentous and invasive growth of Saccharomyces cerevisiae.
abstract: Mitochondrial metabolism is targeted by conserved signaling pathways that mediate external information to the cell. However, less is known about whether mitochondrial dysfunction interferes with signaling and thereby modulates the cellular response to environmental changes. In this study, we analyzed defective filamentous and invasive growth of the yeast Saccharomyces cerevisiae strains that have a dysfunctional mitochondrial genome (rho mutants). We found that the morphogenetic defect of rho mutants was caused by specific downregulation of FLO11, the adhesin essential for invasive and filamentous growth, and did not result from general metabolic changes brought about by interorganellar retrograde signaling. Transcription of FLO11 is known to be regulated by several signaling pathways, including the filamentous-growth-specific MAPK and cAMP-activated protein kinase A (cAMP-PKA) pathways. Our analysis showed that the filamentous-growth-specific MAPK pathway retained functionality in respiratory-deficient yeast cells. In contrast, the cAMP-PKA pathway was downregulated, explaining also various phenotypic traits observed in rho mutants. Thus, our results indicate that dysfunctional mitochondria modulate the output of the conserved cAMP-PKA signaling pathway.
authors.affiliation: Department of Biochemistry, Institute of Molecular and Cell Biology, University of Tartu, Tartu 51010, Estonia.
authors.forename: Anu
authors.initials: A
authors.lastname: Aun
authors.forename: Tiina
authors.initials: T
authors.lastname: Tamm
authors.forename: Juhan
authors.initials: J
authors.lastname: Sedman
mesh_terms: D000242:Cyclic AMP / Q000378:metabolism*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism*; D004256:DNA Polymerase I / Q000235:genetics; D012321:DNA-Directed RNA Polymerases / Q000235:genetics; D015536:Down-Regulation; D020935:MAP Kinase Signaling System; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism; D008928:Mitochondria / Q000235:genetics / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000235:genetics; D009154:Mutation; D010766:Phosphorylation; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000254:growth & development / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic
chemical_list: C110690:FLO11 protein, S cerevisiae; D008562:Membrane Glycoproteins; D024101:Mitochondrial Proteins; D029701:Saccharomyces cerevisiae Proteins; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D012321:DNA-Directed RNA Polymerases; C487996:RPO41 protein, S cerevisiae; D004256:DNA Polymerase I; C068352:MIP1 protein, S cerevisiae