Uloga mitohondrijskih proteina rasprezanja u mehanizmu prijenosa protona kroz unutrašnju mitohondrijsku membranu

doctoral thesis

• Title (english): The role of uncoupling proteins in the proton transfer mechanism across the inner mitochondrial membrane
• Author: Sanja Škulj
• Mentor: Mario Vazdar (mentor)
• Committee member: Branimir Bertoša (predsjednik povjerenstva)
• Committee member: Davor Margetić (član povjerenstva)
• Committee member: Borislav Kovačević (član povjerenstva)
• Granter: University of Zagreb; Faculty of Science; (Department of Chemistry); Zagreb
• Defense date and country: 2020-11-16, Croatia
• Scientific / art field, discipline and subdiscipline: NATURAL SCIENCES; Chemistry
• Universal decimal classification (UDC): 54 - Chemistry. Crystallography. Mineralogy

Abstract

Prijenos protona kroz unutrašnju mitohondrijsku membranu dio je povezanih lančanih
mehanizama koji su važni za normalno usklađeno funkcioniranje organizma. Većinski dio
prijenosa protona odvija se uz pomoć transmembranskih proteina ADP/ATP translokatora
(AAC) i mitohondrijskih proteina rasprezanja (UCP1-5). U radu je naglasak stavljen na
mitohondrijski protein rasprezanja 2 (UCP2) za koji je predložena tercijarna struktura, a čija
glavna uloga je kontrola oksidativnog stresa u organizmu. Uz protein za prijenos protona
potrebna je i dugolančana masna kiselina koja se uz malu energetsku barijeru translocira kroz
unutrašnju mitohondrijsku membranu u neutralnoj formi, dok je povratak anionske forme
potpomognut proteinom. Drugi dio istraživanja vezan je uz utjecaj oksidativnog stresa gdje je
detaljno opisana modelna reakcija produkata lipidne peroksidacije reaktivnih aldehida 4-
hidroksi-2-nonenala (HNE-a) i 4-okso-2-nonenala (ONE-a) s reaktivnim aminokiselinama iz
proteina – lizinom, argininom, histidinom i cisteinom te fosfatidiletanolaminskim (PE) lipidom
koji je sastavni dio unutarnje mitohondrijske membrane.

Abstract (english)

Proton transfer across the inner mitochondrial membrane is part of the related chain
mechanisms that are important for normal functioning of the organism. Majority of proton
transfers are mediated by transmembrane protein ADP/ATP translocator (AAC) and via
mitochondrial uncoupling proteins 1-5 (UCP1-5). This thesis focuses primarily on
mitochondrial uncoupling protein 2 (UCP2) for which we proposed a tertiary structure, and
whose main role is control of the oxidative stress in the body. In addition to the protein
accommodating proton transfer, this process requires a presence of a long chain fatty acid,
which is translocated through the inner mitochondrial membrane in its neutral form with a small
energy barrier. Fatty acid returns to the cytosolic side of the membrane in its anionic form and
this passage is supported by the protein. The second part of the research is related to the
influence of oxidative stress, where we describe in detail the model reactions of two lipid
peroxidation products, i.e. reactive aldehydes 4-hydroxy-2-nonenal (HNE) and 4-oxo-2-
nonenal (ONE), with reactive amino acids from proteins, namely lysine, arginine, histidine and
cysteine as well as phosphatidilethanolamine (PE) lipid which is a constitutive part of inner
mitochonodrial membrane.

• Keywords: transmembranski proteini; UCP2 protein; prijenos protona; masne kiseline; oksidativni stres; MD simulacije; QM računi
• Keywords (english): transmembrane proteins; UCP2 protein; proton transfer; fatty acids; oxidative stress; MD simulations; QM calculations
• Language: croatian
• URN:NBN: urn:nbn:hr:217:020937
• Promotion: 2020
• Study programme: Title: Doctoral study in chemistry; Study programme type: university; Study level: postgraduate; Academic / professional title: doktor/doktorica znanosti, područje prirodnih znanosti, polje kemija (doktor/doktorica znanosti, područje prirodnih znanosti, polje kemija)
• Type of resource: Text
• Extent: 140 str. ; 30 cm
• File origin: Born digital
• Access conditions: Open access
• Created on: 2020-12-08 13:53:31