title: Deletion of the MED13 and CDK8 subunits of the Mediator improves the phenotype of a long-lived respiratory deficient mutant of Podospora anserina.
abstract: In Podospora anserina, the loss of function of the cytochrome segment of the mitochondrial respiratory chain is viable. This is due to the presence in this organism, as in most filamentous fungi, of an alternative respiratory oxidase (AOX) that provides a bypass to the cytochrome pathway. However mutants lacking a functional cytochrome pathway present multiple phenotypes including poorly colored thin mycelium and slow growth. In a large genetic screen based on the improvement of these phenotypes, we isolated a large number of independent suppressor mutations. Most of them led to the constitutive overexpression of the aox gene. In this study, we characterize a new suppressor mutation that does not affect the production of AOX. It is a loss-of-function mutation in the gene encoding the MED13 subunit of the kinase module of the Mediator complex. Inactivation of the cdk8 gene encoding another subunit of the same module also results in partial suppression of a cytochrome-deficient mutant. Analysis of strains lacking the MED13 or CDK8 subunits points to the importance of these subunits as regulators involved in diverse physiological processes such as growth, longevity and sexual development. Interestingly, transcriptional analyses indicate that in P. anserina, loss of the respiratory cytochrome pathway results in the up-regulation of glycolysis-related genes revealing a new type of retrograde regulation. The loss of MED13 augments the up-regulation of some of these genes.
authors.affiliation: Institute for Integrative Biology of the Cell (I2BC), CEA, CNRS, Université Paris-Sud, Avenue de la Terrasse, 91198 Gif-sur-Yvette cedex, France.
authors.forename: Adeline
authors.initials: A
authors.lastname: Humbert
authors.affiliation: Institute for Integrative Biology of the Cell (I2BC), CEA, CNRS, Université Paris-Sud, Avenue de la Terrasse, 91198 Gif-sur-Yvette cedex, France.
authors.forename: Elodie
authors.initials: E
authors.lastname: Bovier
authors.affiliation: Institute for Integrative Biology of the Cell (I2BC), CEA, CNRS, Université Paris-Sud, Avenue de la Terrasse, 91198 Gif-sur-Yvette cedex, France.
authors.forename: Carole H
authors.initials: CH
authors.lastname: Sellem
authors.affiliation: Institute for Integrative Biology of the Cell (I2BC), CEA, CNRS, Université Paris-Sud, Avenue de la Terrasse, 91198 Gif-sur-Yvette cedex, France. Electronic address: annie.sainsard@cgm.cnrs-gif.fr.
authors.forename: Annie
authors.initials: A
authors.lastname: Sainsard-Chanet
mesh_terms: D019069:Cell Respiration; D056850:Cyclin-Dependent Kinase 8 / Q000235:genetics / Q000378:metabolism; D005656:Fungal Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D015966:Gene Expression Regulation, Fungal; D020868:Gene Silencing; D006019:Glycolysis; D018384:Oxidative Stress; D010641:Phenotype; D048468:Podospora / Q000235:genetics* / Q000378:metabolism*; D021122:Protein Subunits; D017384:Sequence Deletion; D014158:Transcription, Genetic
chemical_list: D005656:Fungal Proteins; D021122:Protein Subunits; D056850:Cyclin-Dependent Kinase 8
keywords: Expression of glycolysis genes; Kinase module of Mediator; Podospora anserina; Retrograde regulation