Modifikacija statusa proteostaze: uloga komunikacije između staničnih organela

Perpetual exposure to fluctuating intrinsic and environmental conditions constitute a challenge for maintaining a stable proteome, and this predicament is surmounted by an intricate system of precisely controlled mechanisms that constitute proteostasis. Proteostasis, or protein homeostasis, is orchestrated by an elaborate interlock of signaling pathways collectively known as the proteostasis network, with molecular chaperones constituting its most prominent component. The compartmentalized eukaryotic cell has ascertained organelle-specific chaperones to surmount challenges to proteostasis, and this idiosyncrasy was resolved to be used to study cell-wide effect upon proteostasis modifications in distinct cellular compartments. This study revealed an elaborate cross-organelle communication networking system upon compartmentalized improvement of proteostasis, induced by chaperone enrichment, as well as mild deterioration of proteostasis, induced by chaperone deletions. Comprehensive and detailed experiments confirmed that the improvement of proteostasis, as well as its mild deterioration initiates a cell-wide response which, ultimately, entails replicative lifespan extension, irrespective of the origin of alteration. This research postulates that this cell-wide response is orchestrated by sensing and mediating the protein folding quality status of the proteome in distinct cellular compartments, a response termed here cross-organelle stress response (CORE).Kontinuirana izloženost oscilirajućim uvjetima, unutarnjim i vanjskim, predstavljaju izazov za očuvanjem uravnoteženog proteoma što regulirano proteostatskom mrežom. Najistaknutiji segment navedene mreže su molekularni šaperoni koji uslijed svoje dinamičnosti i raznolikosti omogućavaju stabilizaciju proteina. Separacijom stanice u zasebne odjeljke stečeni su pripadajući šaperoni karakteristični za svaki organel. Kompartmentalizacijom eukariotske stanice je omogućeno uspostavljanje te očuvanje proteostaze u izdvojenim odjeljcima. Ova činjenica je bila poticaj za proučavanje utjecaja poboljšanja i pogoršanja proteostaze u izdvojenim staničnim odjeljcima na stanicu. Obuhvatnim i detaljnim eksperimentima je pokazano da modifikacija proteostaze, bilo delecijom ili overekspresijom pojedinih šaperona, kulminira produljenjem replikativnog životnog vijeka, neovisno o ishodištu same modifikacije. Pretpostavka ovog istraživanja je da je ovaj cijelo-stanični odaziv proveden kroz raspoznavanje i korespondenciju konformacijske vrsnoće proteoma u zasebnim staničnim odjeljcima, odaziv formuliran u ovoj studiji kao odaziv na stres kroz organele (CORE)