Characterization of human VDAC isoforms: a peculiar function for VDAC3?
VDACs are a family of pore-forming proteins mainly located in the mitochondrial outer membrane. In mammals three isoforms exist. In this work we review the information available about them with the addition of new results. We have compared the human VDACs transformed in a yeast strain lacking the endogenous porin. VDAC1 and 2 are able to complement the lack of porin in mitochondrial respiration and modulation of ROS. VDAC3 has a limited ability to support the mitochondrial respiration and has no influence in the control of ROS production. The over-expression of VDAC isoforms in wild type yeast strain led to a dramatic sensitivity to oxidative stress, especially for VDAC3, and a shorter lifespan in respiratory conditions. Real-time PCR comparison of the isoforms indicated that in HeLa cells VDAC1 is 10 times more abundant than VDAC2 and 100 times than VDAC3. The over-expression of any single isoform caused a 10 times increase of the transcripts of VDAC2 and VDAC3, while VDAC1 is not changed by the over-expression of the other isoforms. Models of VDAC2 and VDAC3 isoform structure showed that they could be made of a 19-strand beta-barrel and an N-terminal sequence with variable features. In this work we show for the first time a functional characterization of VDAC3 in a cellular context.
Department of Chemical Sciences, University of Catania, viale A. Doria 6, 95125 Catania, Italy. vdpbiofa@unict.it
Vito
V
De Pinto
Francesca
F
Guarino
Andrea
A
Guarnera
Angela
A
Messina
Simona
S
Reina
Flora M
FM
Tomasello
Vanessa
V
Palermo
Cristina
C
Mazzoni
D000818:Animals; D001483:Base Sequence; D017931:DNA Primers / Q000235:genetics; D006367:HeLa Cells; D006801:Humans; D066298:In Vitro Techniques; D051379:Mice; D008928:Mitochondria / Q000378:metabolism; D033681:Mitochondrial Membrane Transport Proteins; D011487:Protein Conformation; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism; D040681:Structural Homology, Protein; 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*
D017931:DNA Primers; D033681:Mitochondrial Membrane Transport Proteins; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D011994:Recombinant Proteins; C494762:VDAC1 protein, human; C494765:VDAC2 protein, human; C494768:VDAC3 protein, human; C494763:Vdac1 protein, mouse; D050996:Voltage-Dependent Anion Channel 2; D050994:Voltage-Dependent Anion Channels; D050995:Voltage-Dependent Anion Channel 1