Publication details

Insertases scramble lipids: Molecular simulations of MTCH2

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BARTOŠ Ladislav MENON Anant K. VÁCHA Robert

Year of publication 2024
Type Article in Periodical
Magazine / Source Structure
MU Faculty or unit

Central European Institute of Technology

Keywords flip-flop rate; free energy barrier; hydrophilic groove; insertase; membrane defect; molecular dynamics; scramblase
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Description Scramblases play a pivotal role in facilitating bidirectional lipid transport across cell membranes, thereby influencing lipid metabolism, membrane homeostasis, and cellular signaling. MTCH2, a mitochondrial outer membrane protein insertase, has a membrane-spanning hydrophilic groove resembling those that form the lipid transit pathway in known scramblases. Employing both coarse-grained and atomistic molecular dynamics simulations, we show that MTCH2 significantly reduces the free energy barrier for lipid movement along the groove and therefore can indeed function as a scramblase. Notably, the scrambling rate of MTCH2 in silico is similar to that of voltage-dependent anion channel (VDAC), a recently discovered scramblase of the outer mitochondrial membrane, suggesting a potential complementary physiological role for these mitochondrial proteins. Finally, our findings suggest that other insertases which possess a hydrophilic path across the membrane like MTCH2, can also function as scramblases.
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