Visit our Expo - Redox and Inflammation signaling 2012

Session III : Protein kinase cascades as therapeutic targets Poster III, 13
Yeast mitochondrial biogenesis is regulated via the cAMP protein kinase tpk3p
Cyrille Chevztoff, Michel Rigoulet and Anne Devin
IBGC du CNRS, 1 rue Camille Saint Saëns, 33077 BORDEAUX cedex, France. e-mail :
anne.devin@ibgc.u-bordeaux2.fr
In most organisms, the cellular mitochondrial content is modulated by environmental stimuli
and/or in response to energy demand changes. Several cAMP targets and transcription factors
have been shown to be involved in the up-modulation of mitochondrial biogenesis when
energy demand increases. In the yeast Saccharomyces cerevisiae, the Ras/cAMP/protein
kinase pathway is involved in many physiological adaptations of cells upon environmental
changes. Among the adaptation processes occurring during the transition between exponential
growth to stationary phase, the down-modulation of the cytochrome content and of the
respiratory activity of yeast cells plays a role in the maintenance of a high growth yield. The
question is therefore raised as to the role of the Ras/cAMP-protein kinase A pathway in this
adaptative process. We have previously shown that mutant strains exhibiting an increased or
decreased activity of this pathway have a coordinated change in mitochondrial enzyme
content. The question thus arose as to whether a specific kinase might be involved in this
process. We show that out of the three cAMP protein kinases in yeast, tpk3p is the one
involved in mitochondrial biogenesis. Indeed, when grown on non-fermentescible carbon
source TPK3- cells have a significantly decreased amount of mitochondria. Respiratory rates,
enzymatic equipment as well as mitochondrial DNA amount are decreased in this strain.
Mitochondria isolated from the TPK3- strain display distinct energetic features when
compared to the wild type, pointing out a role of Tpk3p in the biogenesis of the mitochondrial
respiratory chain. Moreover, this signaling pathway clearly involves reactive oxygen species,
as shown by the full reversal of the decreased amount of mitochondria in the TPK3- strain by
anti-oxidant. The activity of transcription factors involved in mitochondrial biogenesis is
decreased in the TPK3- strain and restored by anti-oxidant addition, thus indicating that
mitochondria to nucleus signaling might go through reactive oxygen species. This study
points out a crucial role of reactive oxygen species generated in a tpk3p deficient strain for the
adjustment of mitochondrial biogenesis to cellular energy demand.
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