Long-chain fatty acid- and acylcarnitine-bound oxygenated myoglobin interactions with outer mitochondrial membrane
5 affiliations
- 1Department of Biology, University of Maryland , , ,
- 2Duke Human Vaccine Institute, Duke University School of Medicine , , ,
- 3Arkansas Children’s Nutrition Center , , ,
- 4Department of Chemistry and Physics, Drake University , , ,
- 5Department of Food Science Nutrition, Faculty of Applied Sciences, UCSI University , ,
Abstract
Introduction: Oxygenated myoglobin (oxy-Mb) releases oxygen (O2) during interactions with the outer mitochondrial membrane (OMM) and is shown to bind hydrophobic metabolic substrates like palmitate (PLM) and palmitoylcarnitine (PLC). However, it remains unclear how the binding of these specific lipids influences oxy-Mb interaction with the OMM.
Methods: We employed molecular dynamics (MD) simulations to evaluate PLM- and PLC-bound oxy-Mb/membrane interactions in two settings: an average-composition OMM and a cardiolipin-enriched contact-site OMM (CS-OMM). Following steered MD-assisted contact establishment, we assessed unrestrained membrane-association stability and steered detachment forces.
Results: Both PLM- and PLC-bound oxy-Mb, unrestrained after attachment to the membrane, demonstrated a strong preference for the CS-OMM, showing 2.3- to 2.7-fold increases in stability compared to the average-OMM. However, the bound lipid influenced membrane-contact persistence and resistance to steered detachment. PLM-bound oxy-Mb was 10%–20% more stable overall and required approximately twice the detachment force of the PLC-bound complex. During steered detachment, it required roughly twice the force of the PLC-bound complex and preferentially interacted with cardiolipin. Conversely, PLC-bound oxy-Mb exhibited weaker membrane association and preferentially engaged phosphatidylethanolamine and phosphatidylinositol.
Discussion: The identity of the bound lipid actively modulates oxy-Mb’s membrane stability, phospholipid preference, and membrane facing orientation. PLM promotes a more mechanically robust membrane association, whereas PLC produces a distinct and weaker interaction pattern. These structural differences may influence the accessibility of the heme region at the mitochondrial surface; however, O2 release and lipid transfer were not directly measured in the present simulations.
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BibTeX
@article{anishkin2026longchain,
title = {{Long-chain fatty acid- and acylcarnitine-bound oxygenated myoglobin interactions with outer mitochondrial membrane}},
author = {Andriy Anishkin and Sangita Kachhap and Kiran Kumar Adepu and Ryan Sturms and Vaidehi Ulaganathan and Sree V. Chintapalli},
journal = {Frontiers in bioinformatics},
year = {2026},
month = oct,
doi = {10.3389/fbinf.2026.1986755},
url = {https://europepmc.org/article/PMC/PMC13719540},
note = {CC BY},
}
RIS
TY - JOUR
TI - Long-chain fatty acid- and acylcarnitine-bound oxygenated myoglobin interactions with outer mitochondrial membrane
AU - Andriy Anishkin
AU - Sangita Kachhap
AU - Kiran Kumar Adepu
AU - Ryan Sturms
AU - Vaidehi Ulaganathan
AU - Sree V. Chintapalli
PY - 2026
DA - 2026/10/16
JO - Frontiers in bioinformatics
DO - 10.3389/fbinf.2026.1986755
UR - https://europepmc.org/article/PMC/PMC13719540
AB - Introduction: Oxygenated myoglobin (oxy-Mb) releases oxygen (O2) during interactions with the outer mitochondrial membrane (OMM) and is shown to bind hydrophobic metabolic substrates like palmitate (PLM) and palmitoylcarnitine (PLC). However, it remains unclear how the binding of these specific lipids influences oxy-Mb interaction with the OMM. Methods: We employed molecular dynamics (MD) simulations to evaluate PLM- and PLC-bound oxy-Mb/membrane interactions in two settings: an average-composition OMM and a cardiolipin-enriched contact-site OMM (CS-OMM). Following steered MD-assisted contact establishment, we assessed unrestrained membrane-association stability and steered detachment forces. Results: Both PLM- and PLC-bound oxy-Mb, unrestrained after attachment to the membrane, demonstrated a strong preference for the CS-OMM, showing 2.3- to 2.7-fold increases in stability compared to the average-OMM. However, the bound lipid influenced membrane-contact persistence and resistance to steered detachment. PLM-bound oxy-Mb was 10%–20% more stable overall and required approximately twice the detachment force of the PLC-bound complex. During steered detachment, it required roughly twice the force of the PLC-bound complex and preferentially interacted with cardiolipin. Conversely, PLC-bound oxy-Mb exhibited weaker membrane association and preferentially engaged phosphatidylethanolamine and phosphatidylinositol. Discussion: The identity of the bound lipid actively modulates oxy-Mb’s membrane stability, phospholipid preference, and membrane facing orientation. PLM promotes a more mechanically robust membrane association, whereas PLC produces a distinct and weaker interaction pattern. These structural differences may influence the accessibility of the heme region at the mitochondrial surface; however, O2 release and lipid transfer were not directly measured in the present simulations.
SN - 2673-7647
ER -