Naslov
Proton transport across inner mitochondrial membrane assisted with UCP2 protein

Autori
Škulj, Sanja ; Brkljača, Zlatko ; Vazdar, Mario

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, ostalo

Izvornik
Book of abstracts / - , 2019, 142-143

Skup
26. hrvatski skup kemičara i kemijskih inženjera (26HSKIKI) ; 4. simpozij Vladimir Prelog

Mjesto i datum
Šibenik, Hrvatska, 09.04.2019. - 12.04.2019

Vrsta sudjelovanja
Poster

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
molecular dynamics ; UCP2 protein ; proton transport

Sažetak
Proton transport across mitochondrial cell membranes is one of the main metabolic processes in living organism. This transfer from mitochondrial intermembrane space to the mitochondrial matrix across the inner mitochondrial membrane is caused by the existence of the transmembrane proton gradient.1 It is known that long chain fatty acids (LCFA) together with the uncoupling proteins (UCP) participate in the regulation of the transmembrane proton gradient, where UCP catalyzes proton transfer across the inner mitochondrial membrane.2 The mechanism via which UCP protein and FA work together is still unknown and the insight into it will help to better understand the function of mitochondria and cell bioenergetics.3 First, we considered neutral and deprotonated LCFA forms of different length and calculated free energy profiles inside the neat DOPC bilayer using molecular dynamics (MD) simulations. We found that the free energy barriers for the translocation (flip-flop) of neutral and deprotonated forms of fatty acids are approximately 3 kcal mol-1 and 16 kcal mol- 1, respectively. This finding implies that very fast flip-flop of neutral fatty acids across bilayers readily occurs while transport of deprotonated fatty acid is slow and does not occur at the biologically relevant timescale. In order to understand how UCP assists the transport of deprotonated form of LCFA, we simulated mitochondrial uncoupling protein 2 (UCP2) in the DOPC bilayer using advanced MD simulations. The electrostatic potential maps of UCP2 protein indicate the existence of a positively charged surface which could lower free energy barrier for translocation of deprotonated LCFA. Our results are in agreement with cycling protonophoretic mechanism, 2 shedding additional light on this principal biophysical process in mitochondria.

Izvorni jezik
Engleski

Znanstvena područja
Kemija

POVEZANOST RADA