prikaz prve stranice dokumenta Determining the molecular mehanisms regulating lysosome damage and repair pathways
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master's thesis
Determining the molecular mehanisms regulating lysosome damage and repair pathways
Zagreb: University of Zagreb, Faculty of Science, 2018. urn:nbn:hr:217:147253
Božić, Mihaela
University of Zagreb
Faculty of Science
Department of Biology

Institutional repository: Repository of the Faculty of Science

Cite this document

Božić, M. (2018). Determining the molecular mehanisms regulating lysosome damage and repair pathways (Master's thesis). Zagreb: University of Zagreb, Faculty of Science. Retrieved from https://urn.nsk.hr/urn:nbn:hr:217:147253

Božić, Mihaela. "Determining the molecular mehanisms regulating lysosome damage and repair pathways." Master's thesis, University of Zagreb, Faculty of Science, 2018. https://urn.nsk.hr/urn:nbn:hr:217:147253

Božić, Mihaela. "Determining the molecular mehanisms regulating lysosome damage and repair pathways." Master's thesis, University of Zagreb, Faculty of Science, 2018. https://urn.nsk.hr/urn:nbn:hr:217:147253

Božić, M. (2018). 'Determining the molecular mehanisms regulating lysosome damage and repair pathways', Master's thesis, University of Zagreb, Faculty of Science, accessed 22 November 2024, https://urn.nsk.hr/urn:nbn:hr:217:147253

Božić M. Determining the molecular mehanisms regulating lysosome damage and repair pathways [Master's thesis]. Zagreb: University of Zagreb, Faculty of Science; 2018 [cited 2024 November 22] Available at: https://urn.nsk.hr/urn:nbn:hr:217:147253

M. Božić, "Determining the molecular mehanisms regulating lysosome damage and repair pathways", Master's thesis, University of Zagreb, Faculty of Science, Zagreb, 2018. Available at: https://urn.nsk.hr/urn:nbn:hr:217:147253

Metadata
TitleDetermining the molecular mehanisms regulating lysosome damage and repair pathways
Title (croatian)Određivanje molekularnih mehanizama u regulaciji oštećenja i popravka lizosoma
AuthorMihaela Božić
MentorDavid McEwan (mentor)
MentorInga Marijanović (mentor)
Committee memberInga Marijanović (predsjednik povjerenstva)
Committee memberNada Oršolić (član povjerenstva)
Committee memberMaria Špoljar (član povjerenstva)
Committee memberSofia Ana Blažević (član povjerenstva)
GranterUniversity of Zagreb
Faculty of Science
(Department of Biology)
Zagreb
Defense date and country2018-09-28, Croatia
Scientific / art field,
discipline and subdiscipline		NATURAL SCIENCES
Biology
Abstract
Lysosomes are organelles surrounded by a single lipid layer, encapsulating hydrolytic enzymes, and serve as cell’s primary catabolic compartments. Lysosome membranes are easily damaged by the intake of lyososomotropic agents such as L-Leucyl-L-Leucine methyl ester (LLOMe). This event can be recognized by recruitment of Galectin3 to the damaged membranes. Damaged lysosomes can be further repaired, or cleared by autophagy. Autophagic degradation of the lysosomes themselves is termed lysophagy. Little is known of how the cell senses that damage, how it is repaired, or how LLOMe mediated lysosome damage impacts autophagy flux. By overexpressing fluorophore tagged Galectin3 damaged lysosomes can be counted and LLOMe influence characterized. siRNA knock down of specific genes will result in higher number of Galectin3 signal when silenced genes are involved in lysosome damage recognition and repair/clearance. Here, we provide 7 genes identified as possible mediators of the lysosomal biogenesis pathways that can serve as base for future studies and further validation. Identifying those pathways could serve a therapeutic potential in tumours with high levels of cathepsins, inflammations, infections, and neurodegenerative diseases. We also characterize influence of LLOMe intake on autophagy flux, being simultaneously a potent autophagy inducer, and inhibitor of autophagy progression by autophagosome-lysosome fusion.
Abstract (croatian)
Lizosomi su organeli omeđeni jednostukom membranom, sadržavaju hidrolitičke enzime i služe kao primarni katabolički organeli eukariotskih stanica. Lizosomi su vrlo podložni oštećenju pri ulasku lizozomotropnih spojeva, kao što je detergent L-leucil-L-leucin metil ester (LLOMe), u stanicu. Takav događaj može se prepoznati prema regrutaciji proteina Galektin3 na oštećenu membranu lizosoma. Oštećeni lizosomi posljedično bivaju popravljeni ili razgrađeni putem autofagije. Do sada je vrlo malo poznat poces prepoznavanja i popravlja takva oštećenja, te kako oštećenje lizosoma izazvano detergentom LLOMe utječe na process autofagije. Ekspresijom fuzijskog proteina GFP-Galektin3 oštećeni lizosoma mogu se vizualizirati i izbrojati. Utišavanje pojedinih gena pomoću siRNA rezultira u povećanom broju Galektin3 u stanici ako su ti geni uključeni u prepoznavanje oštećenih lizosoma ili njihov popravak/degradaciju. U ovom radu predlažemo 7 gena prepoznatih kao medijatore puta biogeneze lizosoma koji mogu poslužiti kao baza za daljnja istraživanja i detaljnu karakterizaciju staničnih signalnih puteva. Potpuno razumijevanje mehanizma prepoznavanja oštećenih lizosoma i njihovog popravka može poslužiti pri identifikaciji terapeutske mete kod tumora s visokom razinom katepsina, upala, infekcija i neurodegenerativnih bolesti. Također pružamo uvid u utjecaj LLOMe na proces autofagije i označavamo LLOMe kao snažan induktor autofagije, te istovremeno inhibitor napretka progresije autofagije pri koraku fuzije autofagosoma s lizosomom.
Keywords
Keywords (croatian)
Languageenglish
URN:NBNurn:nbn:hr:217:147253
Study programmeTitle: Molecular Biology
Study programme type: university
Study level: graduate
Academic / professional title: magistar/magistra molekularne biologije (magistar/magistra molekularne biologije)
Type of resourceText
File originBorn digital
Access conditionsOpen access
Embargo expiration date: 2020-09-28
Terms of useLicence In copyright icon
Created on2018-10-29 12:00:16