title: Trans-membrane area asymmetry controls the shape of cellular organelles.
abstract: Membrane organelles often have complicated shapes and differ in their volume, surface area and membrane curvature. The ratio between the surface area of the cytosolic and luminal leaflets (trans-membrane area asymmetry (TAA)) determines the membrane curvature within different sites of the organelle. Thus, the shape of the organelle could be critically dependent on TAA. Here, using mathematical modeling and stereological measurements of TAA during fast transformation of organelle shapes, we present evidence that suggests that when organelle volume and surface area are constant, TAA can regulate transformation of the shape of the Golgi apparatus, endosomal multivesicular bodies, and microvilli of brush borders of kidney epithelial cells. Extraction of membrane curvature by small spheres, such as COPI-dependent vesicles within the Golgi (extraction of positive curvature), or by intraluminal vesicles within endosomes (extraction of negative curvature) controls the shape of these organelles. For instance, Golgi tubulation is critically dependent on the fusion of COPI vesicles with Golgi cisternae, and vice versa, for the extraction of membrane curvature into 50-60 nm vesicles, to induce transformation of Golgi tubules into cisternae. Also, formation of intraluminal ultra-small vesicles after fusion of endosomes allows equilibration of their TAA, volume and surface area. Finally, when microvilli of the brush border are broken into vesicles and microvilli fragments, TAA of these membranes remains the same as TAA of the microvilli. Thus, TAA has a significant role in transformation of organelle shape when other factors remain constant.
authors.affiliation: The FIRC Institute of Molecular Oncology, Milan 20139, Italy. galina.beznusenko@ifom.eu.|Consorzio Mario Negri Sud, S. Maria Imbaro, Chieti 66030, Italy. galina.beznusenko@ifom.eu.
authors.forename: Galina V
authors.initials: GV
authors.lastname: Beznoussenko
authors.affiliation: Department of Mathematics, University of Florida, Gainesville, FL 32611-8105, USA. pilyugin@math.ufl.edu.
authors.forename: Sergei S
authors.initials: SS
authors.lastname: Pilyugin
authors.affiliation: Department of Biochemical Physiology, Institute of Biomembranes, 3584 CH Utrecht, The Netherlands. w.geerts@bio.uu.nl.
authors.forename: Willie J C
authors.initials: WJ
authors.lastname: Geerts
authors.affiliation: Department of Physiology and Pharmacology, Tel Aviv University, Tel Aviv 69978, Israel. misha@picard.tau.ac.il.
authors.forename: Michael M
authors.initials: MM
authors.lastname: Kozlov
authors.affiliation: Department of Biochemical Physiology, Institute of Biomembranes, 3584 CH Utrecht, The Netherlands. koert.burger@hccnet.nl.
authors.forename: Koert N J
authors.initials: KN
authors.lastname: Burger
authors.affiliation: Consiglio Nazionale delle Ricerche (CNR), Istituto di Biochimica delle Proteine, Naples 80131, Italy. luini@tigem.it.
authors.forename: Alberto
authors.initials: A
authors.lastname: Luini
authors.affiliation: Institute of Biophysics, University of Ljubljana, 1000 Ljubljana, Slovenia. jure.derganc@mf.uni-lj.si.
authors.forename: Jure
authors.initials: J
authors.lastname: Derganc
authors.affiliation: The FIRC Institute of Molecular Oncology, Milan 20139, Italy. alexandre.mironov@ifom.eu.|Consorzio Mario Negri Sud, S. Maria Imbaro, Chieti 66030, Italy. alexandre.mironov@ifom.eu.
authors.forename: Alexander A
authors.initials: AA
authors.lastname: Mironov
mesh_terms: D000818:Animals; D006367:HeLa Cells; D006801:Humans; D007425:Intracellular Membranes / Q000737:chemistry* / Q000378:metabolism; D008561:Membrane Fusion; D008954:Models, Biological; D021381:Protein Transport; D051381:Rats; D017208:Rats, Wistar