Regulation of Aerobic Energy Metabolism in Podospora anserina by Two Paralogous Genes Encoding Structurally Different c-Subunits of ATP Synthase

PLoS Genet. 2016 Jul 21;12(7):e1006161. doi: 10.1371/journal.pgen.1006161. eCollection 2016 Jul.


Most of the ATP in living cells is produced by an F-type ATP synthase. This enzyme uses the energy of a transmembrane electrochemical proton gradient to synthesize ATP from ADP and inorganic phosphate. Proton movements across the membrane domain (FO) of the ATP synthase drive the rotation of a ring of 8-15 c-subunits, which induces conformational changes in the catalytic part (F1) of the enzyme that ultimately promote ATP synthesis. Two paralogous nuclear genes, called Atp9-5 and Atp9-7, encode structurally different c-subunits in the filamentous fungus Podospora anserina. We have in this study identified differences in the expression pattern for the two genes that correlate with the mitotic activity of cells in vegetative mycelia: Atp9-7 is transcriptionally active in non-proliferating (stationary) cells while Atp9-5 is expressed in the cells at the extremity (apex) of filaments that divide and are responsible for mycelium growth. When active, the Atp9-5 gene sustains a much higher rate of c-subunit synthesis than Atp9-7. We further show that the ATP9-7 and ATP9-5 proteins have antagonist effects on the longevity of P. anserina. Finally, we provide evidence that the ATP9-5 protein sustains a higher rate of mitochondrial ATP synthesis and yield in ATP molecules per electron transferred to oxygen than the c-subunit encoded by Atp9-7. These findings reveal that the c-subunit genes play a key role in the modulation of ATP synthase production and activity along the life cycle of P. anserina. Such a degree of sophistication for regulating aerobic energy metabolism has not been described before.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aerobiosis
  • Energy Metabolism*
  • Enzyme Inhibitors / pharmacology
  • Fungal Proteins / antagonists & inhibitors
  • Fungal Proteins / genetics*
  • Fungal Proteins / metabolism
  • Gene Expression
  • Gene Expression Regulation, Fungal
  • Mitochondrial Proton-Translocating ATPases / antagonists & inhibitors
  • Mitochondrial Proton-Translocating ATPases / genetics*
  • Mitochondrial Proton-Translocating ATPases / metabolism
  • Oligomycins / pharmacology
  • Podospora / enzymology
  • Podospora / genetics*
  • Protein Subunits / antagonists & inhibitors
  • Protein Subunits / genetics
  • Protein Subunits / metabolism


  • Enzyme Inhibitors
  • Fungal Proteins
  • Oligomycins
  • Protein Subunits
  • Mitochondrial Proton-Translocating ATPases

Grants and funding

This work was supported by fundings from the Centre National de la Recherche Scientifique (CNRS) to ASC and JPdR, from the Conseil Régional de la Région Aquitaine and the Agence Nationale de la Recherche to JPdR, from the Paris-Sud University to ASC, and from the Office of the Vice President for Research at Wayne State University to SHA. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.