Inactivation of HAP4 Accelerates RTG -Dependent Osmoadaptation in Saccharomyces cerevisiae .

Mitochondrial (an acronym for ReTroGrade) signaling plays a cytoprotective role under various intracellular or environmental stresses. We have previously shown its contribution to osmoadaptation and capacity to sustain mitochondrial respiration in yeast. Here, we studied the interplay between , the main positive regulator of the pathway, and , encoding the catalytic subunit of the Hap2-5 complex required for the expression of many mitochondrial proteins that function in the tricarboxylic acid (TCA) cycle and electron transport, upon osmotic stress. Cell growth features, mitochondrial respiratory competence, retrograde signaling activation, and TCA cycle gene expression were comparatively evaluated in wild type and mutant cells in the presence and in the absence of salt stress. We showed that the inactivation of improved the kinetics of osmoadaptation by eliciting both the activation of retrograde signaling and the upregulation of three TCA cycle genes: citrate synthase 1 (), aconitase 1 (), and isocitrate dehydrogenase 1 (). Interestingly, their increased expression was mostly dependent on . Impaired respiratory competence in the mutant does not affect its faster adaptive response to stress. These findings indicate that the involvement of the pathway in osmostress is fostered in a cellular context of constitutively reduced respiratory capacity. Moreover, it is evident that the pathway mediates peroxisomes-mitochondria communication by modulating the metabolic function of mitochondria in osmoadaptation.