Mathématiques en biologie et médecine
Ubiquitination feedback during matrix protein import into peroxisomes
Peroxisomes are membrane-bound organelles in eukaryotic cells that post-translationally import folded proteins into their matrix. Import uses a receptor, usually Pex5, that cycles between the cytosol and the peroxisome membrane through a process of docking, ubiquitination, and export while guiding matrix proteins through the import process. Translocation of the protein across the membrane is not well understood and so we consider both uncoupled translocation and directly coupled translocation, as well as a third model we propose, cooperatively coupled translocation. We develop a stochastic computational model of the Pex5 cycle for all three types of translocation and measure the Pex5 and ubiquitin levels on the peroxisomes. Uncoupled and directly coupled translocation behave identically with respect to Pex5 and ubiquitin, with the ubiquitin signal increasing as the matrix protein traffic increases. Cooperatively coupled translocation behaves differently, and yields a ubiquitin signal that decreases with increasing matrix protein traffic, in contrast to the other translocation types. Recent work has shown that ubiquitin on mammalian peroxisome membranes can induce degradation by autophagy. Therefore, the high ubiquitin level for low protein traffic with cooperatively coupled protein translocation could constitute a disuse signal that mediates degradation. This mechanism may be one way that a cell could indirectly regulate peroxisome numbers.
Mardi, 18 juin, 10h30
Salle Du Manège