Role of Lipids and Divalent Cations in Membrane Fusion Mediated by the Heptad Repeat Domain 1 of Mitofusin
Mitochondria are highly dynamic organelles that constantly undergo fusion and fission events to maintain their shape, distribution and cellular function. Mitofusin 1 and 2 proteins are two dynamin-like GTPases involved in the fusion of outer mitochondrial membranes (OMM). Mitofusins are anchored to...
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MDPI AG
2023-09-01
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| Series: | Biomolecules |
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| Online Access: | https://www.mdpi.com/2218-273X/13/9/1341 |
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| author | Anaïs Vlieghe Kristina Niort Hugo Fumat Jean-Michel Guigner Mickaël M. Cohen David Tareste |
| author_facet | Anaïs Vlieghe Kristina Niort Hugo Fumat Jean-Michel Guigner Mickaël M. Cohen David Tareste |
| author_sort | Anaïs Vlieghe |
| collection | DOAJ |
| description | Mitochondria are highly dynamic organelles that constantly undergo fusion and fission events to maintain their shape, distribution and cellular function. Mitofusin 1 and 2 proteins are two dynamin-like GTPases involved in the fusion of outer mitochondrial membranes (OMM). Mitofusins are anchored to the OMM through their transmembrane domain and possess two heptad repeat domains (HR1 and HR2) in addition to their N-terminal GTPase domain. The HR1 domain was found to induce fusion via its amphipathic helix, which interacts with the lipid bilayer structure. The lipid composition of mitochondrial membranes can also impact fusion. However, the precise mode of action of lipids in mitochondrial fusion is not fully understood. In this study, we examined the role of the mitochondrial lipids phosphatidylethanolamine (PE), cardiolipin (CL) and phosphatidic acid (PA) in membrane fusion induced by the HR1 domain, both in the presence and absence of divalent cations (Ca<sup>2+</sup> or Mg<sup>2+</sup>). Our results showed that PE, as well as PA in the presence of Ca<sup>2+</sup>, effectively stimulated HR1-mediated fusion, while CL had a slight inhibitory effect. By considering the biophysical properties of these lipids in the absence or presence of divalent cations, we inferred that the interplay between divalent cations and specific cone-shaped lipids creates regions with packing defects in the membrane, which provides a favorable environment for the amphipathic helix of HR1 to bind to the membrane and initiate fusion. |
| first_indexed | 2024-03-10T22:59:28Z |
| format | Article |
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| institution | Directory Open Access Journal |
| issn | 2218-273X |
| language | English |
| last_indexed | 2024-03-10T22:59:28Z |
| publishDate | 2023-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomolecules |
| spelling | doaj.art-8e0f743856904210bd69e9b25b47b25f2023-11-19T09:45:38ZengMDPI AGBiomolecules2218-273X2023-09-01139134110.3390/biom13091341Role of Lipids and Divalent Cations in Membrane Fusion Mediated by the Heptad Repeat Domain 1 of MitofusinAnaïs Vlieghe0Kristina Niort1Hugo Fumat2Jean-Michel Guigner3Mickaël M. Cohen4David Tareste5Université Paris Cité, Institute of Psychiatry and Neuroscience of Paris (IPNP), Inserm UMR-S 1266, Team Membrane Traffic in Healthy & Diseased Brain, 75014 Paris, FranceUniversité Paris Cité, Institute of Psychiatry and Neuroscience of Paris (IPNP), Inserm UMR-S 1266, Team Membrane Traffic in Healthy & Diseased Brain, 75014 Paris, FranceUniversité Paris Cité, Institute of Psychiatry and Neuroscience of Paris (IPNP), Inserm UMR-S 1266, Team Membrane Traffic in Healthy & Diseased Brain, 75014 Paris, FranceSorbonne Université, Institut de Minéralogie, de Physique des Matériaux et de Cosmochimie (IMPMC), CNRS UMR 7590, MNHN, IRD UR 206, 75005 Paris, FranceSorbonne Université, Institut de Biologie Physico-Chimique (IBPC), CNRS UMR 8226, Laboratoire de Biologie Moléculaire et Cellulaire des Eucaryotes, 75005 Paris, FranceUniversité Paris Cité, Institute of Psychiatry and Neuroscience of Paris (IPNP), Inserm UMR-S 1266, Team Membrane Traffic in Healthy & Diseased Brain, 75014 Paris, FranceMitochondria are highly dynamic organelles that constantly undergo fusion and fission events to maintain their shape, distribution and cellular function. Mitofusin 1 and 2 proteins are two dynamin-like GTPases involved in the fusion of outer mitochondrial membranes (OMM). Mitofusins are anchored to the OMM through their transmembrane domain and possess two heptad repeat domains (HR1 and HR2) in addition to their N-terminal GTPase domain. The HR1 domain was found to induce fusion via its amphipathic helix, which interacts with the lipid bilayer structure. The lipid composition of mitochondrial membranes can also impact fusion. However, the precise mode of action of lipids in mitochondrial fusion is not fully understood. In this study, we examined the role of the mitochondrial lipids phosphatidylethanolamine (PE), cardiolipin (CL) and phosphatidic acid (PA) in membrane fusion induced by the HR1 domain, both in the presence and absence of divalent cations (Ca<sup>2+</sup> or Mg<sup>2+</sup>). Our results showed that PE, as well as PA in the presence of Ca<sup>2+</sup>, effectively stimulated HR1-mediated fusion, while CL had a slight inhibitory effect. By considering the biophysical properties of these lipids in the absence or presence of divalent cations, we inferred that the interplay between divalent cations and specific cone-shaped lipids creates regions with packing defects in the membrane, which provides a favorable environment for the amphipathic helix of HR1 to bind to the membrane and initiate fusion.https://www.mdpi.com/2218-273X/13/9/1341mitochondriamembranefusionMitofusinamphipathic helixdivalent cations |
| spellingShingle | Anaïs Vlieghe Kristina Niort Hugo Fumat Jean-Michel Guigner Mickaël M. Cohen David Tareste Role of Lipids and Divalent Cations in Membrane Fusion Mediated by the Heptad Repeat Domain 1 of Mitofusin Biomolecules mitochondria membrane fusion Mitofusin amphipathic helix divalent cations |
| title | Role of Lipids and Divalent Cations in Membrane Fusion Mediated by the Heptad Repeat Domain 1 of Mitofusin |
| title_full | Role of Lipids and Divalent Cations in Membrane Fusion Mediated by the Heptad Repeat Domain 1 of Mitofusin |
| title_fullStr | Role of Lipids and Divalent Cations in Membrane Fusion Mediated by the Heptad Repeat Domain 1 of Mitofusin |
| title_full_unstemmed | Role of Lipids and Divalent Cations in Membrane Fusion Mediated by the Heptad Repeat Domain 1 of Mitofusin |
| title_short | Role of Lipids and Divalent Cations in Membrane Fusion Mediated by the Heptad Repeat Domain 1 of Mitofusin |
| title_sort | role of lipids and divalent cations in membrane fusion mediated by the heptad repeat domain 1 of mitofusin |
| topic | mitochondria membrane fusion Mitofusin amphipathic helix divalent cations |
| url | https://www.mdpi.com/2218-273X/13/9/1341 |
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