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Deletion of Voltage-Dependent Anion Channel 1 knocks mitochondria down triggering metabolic rewiring in yeast

  • Andrea Magrì
  • Maria Carmela Di Rosa
  • Ivan Orlandi
  • Francesca Guarino
  • Simona Reina
  • Maria Guarnaccia
  • Giovanna Morello
  • Antonio Spampinato
  • Sebastiano Cavallaro
  • Angela Messina
  • Marina VaiEmail author
  • Vito De PintoEmail author
Original Article

Abstract

The Voltage-Dependent Anion-selective Channel (VDAC) is the pore-forming protein of mitochondrial outer membrane, allowing metabolites and ions exchanges. In Saccharomyces cerevisiae, inactivation of POR1, encoding VDAC1, produces defective growth in the presence of non-fermentable carbon source. Here, we characterized the whole-genome expression pattern of a VDAC1-null strain (Δpor1) by microarray analysis, discovering that the expression of mitochondrial genes was completely abolished, as consequence of the dramatic reduction of mtDNA. To overcome organelle dysfunction, Δpor1 cells do not activate the rescue signaling retrograde response, as ρ0 cells, and rather carry out complete metabolic rewiring. The TCA cycle works in a “branched” fashion, shunting intermediates towards mitochondrial pyruvate generation via malic enzyme, and the glycolysis-derived pyruvate is pushed towards cytosolic utilization by PDH bypass rather than the canonical mitochondrial uptake. Overall, Δpor1 cells enhance phospholipid biosynthesis, accumulate lipid droplets, increase vacuoles and cell size, overproduce and excrete inositol. Such unexpected re-arrangement of whole metabolism suggests a regulatory role of VDAC1 in cell bioenergetics.

Keywords

Warburg effect Inositol Fatty acids Porin Retrograde signaling PDH bypass Mitochondrial DNA 

Notes

Acknowledgements

VDP acknowledges the financial support by MIUR (PRIN 2015795S5W_005) and University of Catania (Piano Triennale Ricerca). MV acknowledges the financial support by Cariplo Foundation 2015-0641. The authors acknowledge the support of Dr. Giulia Gentile for the initial experimental design of microarray analysis.

Supplementary material

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Supplementary material 1 (XLSX 1082 kb)
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Supplementary material 2 (XLSX 18 kb)
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Supplementary material 3 (DOCX 3505 kb)

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Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Andrea Magrì
    • 1
    • 2
    • 3
  • Maria Carmela Di Rosa
    • 1
    • 3
  • Ivan Orlandi
    • 4
  • Francesca Guarino
    • 1
    • 3
  • Simona Reina
    • 1
    • 2
    • 3
  • Maria Guarnaccia
    • 5
  • Giovanna Morello
    • 5
  • Antonio Spampinato
    • 5
  • Sebastiano Cavallaro
    • 5
  • Angela Messina
    • 2
    • 3
  • Marina Vai
    • 4
    Email author
  • Vito De Pinto
    • 1
    • 3
    Email author
  1. 1.Department of Biomedical and Biotechnological SciencesUniversity of CataniaCataniaItaly
  2. 2.Department of Biological, Geological and Environmental SciencesUniversity of CataniaCataniaItaly
  3. 3.National Institute of Biostructures and Biosystems (INBB)Section of CataniaRomeItaly
  4. 4.Department of Biotechnologies and BiosciencesUniversity of Milano-BicoccaMilanItaly
  5. 5.Institute for Biomedical Research and Innovation (IRIB)National Research Council (CNR)CataniaItaly

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