Uloga fosfataze PGAM5 u mitofagiji posredovanoj BNIP3L/NIX receptorom

master's thesis

• Title (english): Role of PGAM5 phosphatase in BNIP3L/NIX receptor-mediated mitophagia
• Author: Klara Ivanišević
• Mentor: Ivana Novak Nakir (mentor)
• Mentor: Nada Oršolić (komentor)
• Committee member: Nada Oršolić (predsjednik povjerenstva)
• Committee member: Silvija Černi (član povjerenstva)
• Committee member: Jasna Lajtner (član povjerenstva)
• Committee member: Maja Matulić (član povjerenstva)
• Granter: University of Zagreb; Faculty of Science; (Department of Biology); Zagreb
• Defense date and country: 2023-02-28, Croatia
• Scientific / art field, discipline and subdiscipline: NATURAL SCIENCES; Biology

Abstract

Dosadašnja istraživanja su pokazala kako je dimerizacija receptora BNIP3L/NIX molekularni
mehanizam koji pospješuje mitofagiju posredovanu receptorom. Stvaranjem homodimera,
BNIP3L/NIX receptor pojačano regrutira autofagosome. Kako bi se razjasnio mehanizam
dimerizacije, identificiran je serin na poziciji 212, kao najvažnija aminokiselina na Cterminalnom kraju BNIP3L/NIX receptora odgovorna za dimerizaciju. Eksperimentalno je
pokazano da fosforilacija serina 212 sprječava stvaranje dimera BNIP3L/NIX receptora.
Pretraživanjem literature definirane su potencijalne fosfataze C-terminalnog kraja receptora
BNIP3L/NIX, a među njima je bila i fosfataza PGAM5 čije se djelovanje nastojalo istražiti.
Cilj ovog istraživanja je bio otkriti ima li PGAM5 ulogu u defosforilaciji serina 212 što bi
razjasnilo jedan od mehanizama regulacije mitofagije. Metodama pull-down i
koimunoprecipitacije analizirana je interakcija fosfataze PGAM5 s fuzioniranim proteinom
EGFP-BNIP3L/NIX i njegovim mutantama BNIP3L/NIX-S212A i BNIP3L/NIX-S212E.
Dobiveni rezultati dokazali su interakciju receptora BNIP3L/NIX s fosfatazom PGAM5.

Abstract (english)

Previous research has shown that dimerization of the BNIP3L/NIX recepotr is a molecular
mechanism that promotes receptor-mediated. Formation of a BNIP3L/NIX homodimer
increases recruitment of mitochondria to autophagosomes. To elucidate the mechanism of
dimerization, serine at position 212 was identified as the most important amino acid at the Cterminal end of the BNIP3L/NIX for dimerization. It was shown that serine 212
phosphorylation prevents the formation of BNIP3L/NIX dimers. By searching the literature,
potential phosphatases of the C-terminal end of the BNIP3L/NIX receptor were defined, and
among them was the PGAM5 phosphatase, whose activity was investigated in this master
thesis. The aim of this research was to find whether PGAM5 has a role in the dephosphorylation
of serine 212, which would clarify one of the mechanisms of mitophagy regulation. The
interaction of the phosphatase PGAM5 with the fusion protein EGFP-BNIP3L/NIX and its
mutants BNIP3L/NIX-S212A and BNIP3L/NIX-S212E was analyzed using pull-down and coimmunoprecipitation. The results have shown that BNIP3L/NIX is interacting with
phosphatase PGAM5.

• Keywords: autofagija; mitofagija; BNIP3L/NIX; dimerizacija; PGAM5
• Keywords (english): autophagy; mitophagy; BNIP3L/NIX; dimerization; PGAM5
• Language: croatian
• URN:NBN: urn:nbn:hr:217:656028
• Study programme: Title: Experimental Biology; Study programme type: university; Study level: graduate; Academic / professional title: magistar/magistra eksperimentalne biologije (magistar/magistra eksperimentalne biologije)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Embargoed access; Embargo expiration date: 2025-02-28
• Created on: 2023-03-08 11:41:00