Yeast growth in raffinose results in resistance to acetic-acid induced programmed cell death mostly due to the activation of the mitochondrial retrograde pathway.

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Abstract

In order to investigate whether and how a modification of mitochondrialmetabolism can affect yeast sensitivityto programmed cell death (PCD) induced by acetic acid (AA-PCD), yeast cells were grown on raffinose, as a sole carbon source, which, differently from glucose, favours mitochondrial respiration. We found that, differently from glucose-grown cells, raffinose-grown cells were mostly resistant to AA-PCD and that this was due to the activation of mitochondrial retrograde (RTG) response, which increased with time, as revealed by the upregulationof the peroxisomal isoform of citrate synthase and isocitrate dehydrogenase isoform 1, RTG pathwaytarget genes. Accordingly, the deletion of RTG2 and RTG3, a positive regulator and a transcription factor of the RTG pathway, resulted in AA-PCD, as shown by TUNEL assay. Neither deletion in raffinose-grown cells of HAP4,encoding the positive regulatory subunit of the Hap2,3,4,5 complex nor constitutive activation of the RTG pathway in glucose-grown cells due to deletion of MKS1, a negative regulator of RTG pathway, had effect on yeast AA-PCD. The RTG pathway was found to be activated in yeast cells containing mitochondria, in which membrane potential wasmeasured, capable to consume oxygen in amanner stimulated by the uncoupler CCCP and inhibited by the respiratory chain inhibitor antimycin A. AA-PCD resistance in raffinose-grown cells occurs with a decrease in both ROS production and cytochrome c release as compared to glucose-grown cells en route to AA-PCD.

Autore Pugliese

Tutti gli autori

  • Guaragnella N.; Zdralevi M.; Lattanzio P.; Marzulli D.; Pracheil T.; Liu Z.; Passarella S.; Marra E.; Giannattasio S.

Titolo volume/Rivista

Biochimica et biophysica acta. Molecular cell research

Anno di pubblicazione

2013

ISSN

0167-4889

ISBN

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