Distribution and dynamics of quinones in the lipid bilayer mimicking the inner membrane of mitochondria

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• 作者：Petri Kaurola^a ; Vivek Sharma^a ; ^b ; Amanda Vonk^a ; Ilpo Vattulainen^a ; ^b ; ^c ; Tomasz Ró ; g^a ; ^b ; ^{tomasz.rog@helsinki.fi" class="auth_mail" title="E-mail the corresponding author}
• 关键词：MD ; molecular dynamics ; US ; umbrella sampling ; WHAM ; weighted histogram analysis method ; PMF ; potential of mean force ; Q ; quinone or its analogue ; PC ; phosphatidylcholine ; PE ; phosphatidylethanolamine ; CL ; cardiolipin
• 刊名：Biochimica et Biophysica Acta (BBA)-Biomembranes
• 出版年：2016
• 出版时间：September 2016
• 年：2016
• 卷：1858
• 期：9
• 页码：2116-2122
• 全文大小：1384 K

文摘

Quinone and its analogues (Q) constitute an important class of compounds that perform key electron transfer reactions in oxidative- and photo-phosphorylation. In the inner membrane of mitochondria, ubiquinone molecules undergo continuous redox transitions enabling electron transfer between the respiratory complexes. In such a dynamic system undergoing continuous turnover for ATP synthesis, an uninterrupted supply of substrate molecules is absolutely necessary. In the current work, we have performed atomistic molecular dynamics simulations and free energy calculations to assess the structure, dynamics, and localization of quinone and its analogues in a lipid bilayer, whose composition mimics the one in the inner mitochondrial membrane. The results show that there is a strong tendency of both quinone and quinol molecules to localize in the vicinity of the lipids' acyl groups, right under the lipid head group region. Additionally, we observe a second location in the middle of the bilayer where quinone molecules tend to stabilize. Translocation of quinone through a lipid bilayer is very fast and occurs in 10–100 ns time scale, whereas the translocation of quinol is at least an order of magnitude slower. We suggest that this has important mechanistic implications given that the localization of Q ensures maximal occupancy of the Q-binding sites or Q-entry points in electron transport chain complexes, thereby maintaining an optimal turnover rate for ATP synthesis.