The potential mechanism of methamphetamine-induced mitochondrial dysfunction and cell degeneration via direct permeation across mitochondrial membranes: The study on molecular dynamics simulations and in vitro model
2
Issued Date
2025-12-01
Resource Type
eISSN
18736351
Scopus ID
2-s2.0-105019272229
Pubmed ID
40962044
Journal Title
Food and Chemical Toxicology an International Journal Published for the British Industrial Biological Research Association
Volume
206
Rights Holder(s)
SCOPUS
Bibliographic Citation
Food and Chemical Toxicology an International Journal Published for the British Industrial Biological Research Association Vol.206 (2025) , 115743
Suggested Citation
Polvat T., Khuntawee W., Prasertporn T., Promthep K., Kerdkaen N., Panmanee J., Nalakarn P., Wong-Ekkabut J., Chetsawang B. The potential mechanism of methamphetamine-induced mitochondrial dysfunction and cell degeneration via direct permeation across mitochondrial membranes: The study on molecular dynamics simulations and in vitro model. Food and Chemical Toxicology an International Journal Published for the British Industrial Biological Research Association Vol.206 (2025) , 115743. doi:10.1016/j.fct.2025.115743 Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/112767
Title
The potential mechanism of methamphetamine-induced mitochondrial dysfunction and cell degeneration via direct permeation across mitochondrial membranes: The study on molecular dynamics simulations and in vitro model
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Corresponding Author(s)
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Abstract
This study aims to investigate the direct permeation of methamphetamine (METH)-induced mitochondrial dysfunction leading to apoptotic cell death. The molecular dynamics (MD) simulations were performed to study METH and dopamine (DA) penetration through phospholipid membranes, which are abundant on the cellular and mitochondrial membranes. The simulation results showed that METH molecules passively diffuse into the membranes, whereas the DA molecule adsorbs onto the lipid bilayer interface. Additionally, the number of H-bond formations and the distribution lifetime of METH were higher than those of DA. Furthermore, the potential of mean force (PMF) profiles for METH and DA translocating through the lipid bilayer were calculated. The result demonstrated that the free energy barrier of METH is small, and the lowest free energy is located inside the bilayer. On the other hand, a significant energy barrier was found at the bilayer center in the PMF profile of DA. The simulation results suggest that METH can passively penetrate through the lipid bilayer. METH-induced mitochondrial dysfunction leading to cell death was observed in both dopamine transporter (DAT)-expressing cells and non-DAT-expressing cells. This finding highlights the direct permeation of METH across the membrane, inducing impairment of mitochondrial function and cell degeneration.