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Interaction between goniothalamin and peroxisomal multifunctional enzyme type 2 triggering endoplasmic reticulum
Thanet Sophonnithiprasert1, Ornjira Aruksakunwong2, Etsu Tashiro3
1Biochemistry Unit, Department of Medical Sciences, Faculty of Science, Rangsit University, Pathum Thani 12000, Thailand.
Heliyon
|October 26, 2020
Summary
Goniothalamin, a plant compound, triggers endoplasmic reticulum (ER) stress by binding to the MFE2 enzyme. This interaction disrupts lipid metabolism, leading to ER stress and apoptosis.
Area of Science:
- Biochemistry
- Cell Biology
- Pharmacology
Background:
- Endoplasmic reticulum (ER) stress is a cellular response implicated in cytotoxicity.
- Styryllactone compounds, like goniothalamin from *Goniothalamus spp*., are known for their biological activities.
Purpose of the Study:
- To investigate the mechanism by which goniothalamin induces ER stress in HeLa cells.
- To identify specific goniothalamin-binding proteins and elucidate their role in ER stress.
Main Methods:
- *In vitro* goniothalamin-linked bead pull-down assay to identify binding proteins.
- Computational molecular docking to confirm goniothalamin-MFE2 interaction.
- siRNA-mediated knockdown of MFE2 to assess its role in ER stress induction.
Main Results:
- Goniothalamin specifically binds to peroxisomal multifunctional enzyme type 2 (MFE2).
- Molecular docking confirmed goniothalamin binding to MFE2's scp-2, enoyl-CoA hydratase 2, and dehydrogenase domains.
- MFE2 knockdown reduced the expression of CHOP, a key mediator of ER stress-induced apoptosis.
- Goniothalamin binding to MFE2 appears to perturb lipid metabolism, activating the unfolded protein response.
Conclusions:
- Goniothalamin directly binds to MFE2, a key enzyme in fatty acid metabolism.
- This interaction likely disrupts MFE2 function, leading to lipid metabolism perturbation and ER stress.
- The study provides the first evidence of goniothalamin-induced ER stress mediated by MFE2 and lipid metabolism changes.
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