title: Interplay of packing and flip-flop in local bilayer deformation. How phosphatidylglycerol could rescue mitochondrial function in a cardiolipin-deficient yeast mutant.
abstract: In a previous work, we have shown that a spatially localized transmembrane pH gradient, produced by acid micro-injection near the external side of cardiolipin-containing giant unilamellar vesicles, leads to the formation of tubules that retract after the dissipation of this gradient. These tubules have morphologies similar to mitochondrial cristae. The tubulation effect is attributable to direct phospholipid packing modification in the outer leaflet, that is promoted by protonation of cardiolipin headgroups. In this study, we compare the case of cardiolipin-containing giant unilamellar vesicles with that of giant unilamellar vesicles that contain phosphatidylglycerol (PG). Local acidification also promotes formation of tubules in the latter. However, compared with cardiolipin-containing giant unilamellar vesicles the tubules are longer, exhibit a visible pearling, and have a much longer lifetime after acid micro-injection is stopped. We attribute these differences to an additional mechanism that increases monolayer surface imbalance, namely inward PG flip-flop promoted by the local transmembrane pH gradient. Simulations using a fully nonlinear membrane model as well as geometrical calculations are in agreement with this hypothesis. Interestingly, among yeast mutants deficient in cardiolipin biosynthesis, only the crd1-null mutant, which accumulates phosphatidylglycerol, displays significant mitochondrial activity. Our work provides a possible explanation of such a property and further emphasizes the salient role of specific lipids in mitochondrial function.
authors.affiliation: UPMC Université Paris 06, UMR 168, Institut Curie, Paris, France; CNRS, UMR 168, Institut Curie, Paris, France.
authors.forename: Nada
authors.initials: N
authors.lastname: Khalifat
authors.affiliation: Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, New Jersey.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Rahimi
authors.affiliation: Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, New Jersey; Department of Physics, Princeton University, Princeton, New Jersey.
authors.forename: Anne-Florence
authors.initials: AF
authors.lastname: Bitbol
authors.affiliation: Université Paris Diderot-Paris 7, Matière et Systèmes Complexes CNRS UMR 7057, Paris, France. Electronic address: michel.seigneuret@univ-paris-diderot.fr.
authors.forename: Michel
authors.initials: M
authors.lastname: Seigneuret
authors.affiliation: Université Paris Diderot-Paris 7, Matière et Systèmes Complexes CNRS UMR 7057, Paris, France.
authors.forename: Jean-Baptiste
authors.initials: JB
authors.lastname: Fournier
authors.affiliation: Université Paris Diderot-Paris 7, Matière et Systèmes Complexes CNRS UMR 7057, Paris, France; Department of Physics-UFR 925, Université Pierre et Marie Curie, Paris, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Puff
authors.affiliation: Departament de Matemàtica Aplicada III, LaCàN, Universitat Politècnica de Catalunya, Barcelona, Spain.
authors.forename: Marino
authors.initials: M
authors.lastname: Arroyo
authors.affiliation: Université Paris Diderot-Paris 7, Matière et Systèmes Complexes CNRS UMR 7057, Paris, France; Department of Physics-UFR 925, Université Pierre et Marie Curie, Paris, France. Electronic address: miglena.anguelova@upmc.fr.
authors.forename: Miglena I
authors.initials: MI
authors.lastname: Angelova
mesh_terms: D000465:Algorithms; D002308:Cardiolipins / Q000737:chemistry*; D003198:Computer Simulation; D006863:Hydrogen-Ion Concentration; D007093:Imidazoles; D007700:Kinetics; D008051:Lipid Bilayers / Q000737:chemistry; D008845:Microinjections; D008856:Microscopy, Fluorescence; D008928:Mitochondria / Q000502:physiology; D017711:Nonlinear Dynamics; D010715:Phosphatidylglycerols / Q000737:chemistry*; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism; D053835:Unilamellar Liposomes / Q000737:chemistry*; D014741:Video Recording
chemical_list: D002308:Cardiolipins; D007093:Imidazoles; D008051:Lipid Bilayers; D010715:Phosphatidylglycerols; D029701:Saccharomyces cerevisiae Proteins; D053835:Unilamellar Liposomes; C573109:mutaprodenafil