Tuesday, 21 November 2017
UNIT CELLULAR HOMEOSTASIS AND ADAPTATION TO STRESS  

 

Our main interest is to understand the molecular mechanisms that allow cells to respond, adapt and survive in adverse environmental conditions. Our group investigates signaling pathways and different levels of physiological adaptation to chemical stress in model systems such as the yeast Saccharomyces cerevisiae. Currently we conduct two main lines of investigation that focus on organelle homeostasis (mitochondria and peroxisomes) and the dynamic regulation of gene expression in response to stress.

 

1) Stress regulated homeostasis and dynamics of mitochondria and peroxisomes. Maintaining healthy organelles such as mitochondria or peroxisomes is an essential function of all eukaryotic cells. Furthermore, biomass, morphology and biochemical functions of the two organelles are regulated by numerous external stimuli. The deregulation of mitochondrial homeostasis is closely linked to oxidative damage, cellular aging and neurodegenerative diseases in humans. Our group studies mitochondrial dynamics in the yeast model. Our recent studies show that stress adaptation requires a selective mitochondrial activation, which in the case of the pyruvate transporter Mpc requires the coordinated regulation of specific subunits of the complex. High respiratory activity and/or loss of mitochondrial membrane potential also increases the rate of degradation of specific sub-complexes of the mitochondrial electron transport chain. Our results show that there are mechanisms of selective mitophagy in these conditions and our current research focuses on deciphering the molecular mechanisms of this process of mitochondrial recycling. The peroxisome is another organelle which undergoes a controlled activation under stress. Peroxisome number increases rapidly and its function is essential upon ionic stress conditions. Our group investigates signaling pathways and possible mechanisms (de novo biogenesis, fission etc) of this peroxisomal regulation especially in the yeast model.

 

2) Dynamic transcriptional modulation in response to chemical stress. The regulation of gene expression is a universal mode of defense against many types of stress. Transcriptional activation is an extremely dynamic process that is modulated by the degree of stimulation and the physiological state, the history and the defense resources of the cell. Our group has developed techniques to monitor accurately and quantitatively the modulation of gene expression in real time in living yeast cells. Currently we focus these approaches to decipher the mechanisms that allow a gradual adaptation to different stresses, to determine the effects of memory on the transcriptional response and determine the components of the differential response to different drugs and toxins. At the same time, the transcriptional profile of a cell to a stimulus can extract information on its sensitivity to stress. These approaches are now being applied to understanding the mechanisms of toxicity of different chemicals and to unravel physiological determinants of stress defense.

 

 Investigador Principal:

 Markus Proft

 
 

Currículum Vitae

Publicaciones

Teléfono: 963391769
Email: mproftibv.csic.es 

 
     
 
  • Proft, Markus
  • Alarcón Hernandis, Benito