Characterization of the autophagic process induced by the protein tmem59

Resumen

Autophagy is a cell-autonomous catabolic process; it performs a regulated lysosomal degradation of cellular constituens from single proteins to whole organelles: Historically, autophagy has been seen as an in-bulk degradation process, however, more recently the selectivity and specificity of diverse autophagic processes have became evident (Flimia et al., 2013) and the molecular machinery has just been discovering ( Johansen and Lamark, 2010) Molecuolar machinery and basic regulation of the autopahgy pathway are conserved in all eukaryotes, in essence mTOR and the ATG core proteins (Levine and Ranganathan, 2010). However, in mammals, the autophagic procesese have acquire more important functions beypond the basal autophagy to maintain the cytosol free of damnging and surplus components and the starvation-induced autophagy to recycle constituents and redirect cellular resources to maintain cllular/whole organism viability (Mizusxhima and Levine, 2010). Therefore, the autophagic regulatino has turned to be more complicated than in yeast (Yang an Klionsky, 2010) and only until recently is been revealed. Some time ago, a screening to discover new human proteins involved in the regulation of different cell death pathways vas carried out in Dr. Pimentel-Muiós lab (Alcala et al., 2008). Some of the newly discovered clones produced a sort of cell death with intense vacuolation and this phenotype has been implicated previously with autophagic cell death (Shimizu et al., 2004). Particulary, one of this clone was encoded TMEM59, a type-I transmembrane protein with an unknown functio. Type-I transmembrane protein usually functions a receptors and they have been highlighted has potentially drug targets (Chou and Elrod, 1999). Earlier stuides narrowed down the region responsible of the autophagy capacity of TMEM59 to a minimal peptide. Therefore it may be a good candidate to further extend some studies relative to its function in autophagic pathways and its role mammalian patho-physiology