title: Role of cysteines in mammalian VDAC isoforms' function.
abstract: In this mini-review, we analyze the influence of cysteines in the structure and activity of mitochondrial outer membrane mammalian VDAC isoforms. The three VDAC isoforms show conserved sequences, similar structures and the same gene organization. The meaning of three proteins encoded in different chromosomes must thus be searched for subtle differences at the amino acid level. Among others, cysteine content is noticeable. In humans, VDAC1 has 2, VDAC2 has 9 and VDAC3 has 6 cysteines. Recent works have shown that, at variance from VDAC1, VDAC2 and VDAC3 exhibit cysteines predicted to protrude towards the intermembrane space, making them a preferred target for oxidation by ROS. Mass spectrometry in VDAC3 revealed that a disulfide bridge can be formed and other cysteine oxidations are also detectable. Both VDAC2 and VDAC3 cysteines were mutagenized to highlight their role in vitro and in complementation assays in Δporin1 yeast. Chemico-physical techniques revealed an important function of cysteines in the structural stabilization of the pore. In conclusion, the works available on VDAC cysteines support the notion that the three proteins are paralogs with a similar pore-function and slightly different, but important, ancillary biological functions. This article is part of a Special Issue entitled 'EBEC 2016: 19th European Bioenergetics Conference, Riva del Garda, Italy, July 2-6, 2016', edited by Prof. Paolo Bernardi.
authors.affiliation: Department of Biomedicine and Biotechnology BIOMETEC, Section of Biology and Genetics, University of Catania, Italy; National Institute for Biomembranes and Biosystems, Section of Catania, Italy. Electronic address: vdpbiofa@unict.it.
authors.forename: Vito
authors.initials: V
authors.lastname: De Pinto
authors.affiliation: Department of Biomedicine and Biotechnology BIOMETEC, Section of Biology and Genetics, University of Catania, Italy; National Institute for Biomembranes and Biosystems, Section of Catania, Italy; Department of Biological, Geological and Environmental Sciences, Section of Molecular Biology, University of Catania, Italy.
authors.forename: Simona
authors.initials: S
authors.lastname: Reina
authors.affiliation: Molecular Biophysics Laboratory, Department of Biological Sciences, Indian Institute of Science Education and Research, Bhopal, India.
authors.forename: Ankit
authors.initials: A
authors.lastname: Gupta
authors.affiliation: National Institute for Biomembranes and Biosystems, Section of Catania, Italy; Department of Biological, Geological and Environmental Sciences, Section of Molecular Biology, University of Catania, Italy.
authors.forename: Angela
authors.initials: A
authors.lastname: Messina
authors.affiliation: Molecular Biophysics Laboratory, Department of Biological Sciences, Indian Institute of Science Education and Research, Bhopal, India.
authors.forename: Radhakrishnan
authors.initials: R
authors.lastname: Mahalakshmi
mesh_terms: D000818:Animals; D017124:Conserved Sequence; D003545:Cysteine / Q000378:metabolism*; D019143:Evolution, Molecular; D015870:Gene Expression; D006801:Humans; D017136:Ion Transport; D008928:Mitochondria / Q000378:metabolism; D033681:Mitochondrial Membrane Transport Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D051336:Mitochondrial Membranes / Q000378:metabolism*; D008958:Models, Molecular; D009154:Mutation; D055503:Protein Multimerization; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism; D050995:Voltage-Dependent Anion Channel 1 / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D050996:Voltage-Dependent Anion Channel 2 / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D050994:Voltage-Dependent Anion Channels / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism
chemical_list: D033681:Mitochondrial Membrane Transport Proteins; C494762:VDAC1 protein, human; C494765:VDAC2 protein, human; C494768:VDAC3 protein, human; D050996:Voltage-Dependent Anion Channel 2; D050994:Voltage-Dependent Anion Channels; D050995:Voltage-Dependent Anion Channel 1; D003545:Cysteine