%0 Journal Article
%T Two-color STED microscopy reveals different degrees of colocalization between hexokinase-I and the three human VDAC isoforms
%A Daniel Neumann
%A Johanna B¨ąckers
%A Lars Kastrup
%A Stefan W Hell
%A Stefan Jakobs
%J BMC Biophysics
%D 2010
%I BioMed Central
%R 10.1186/1757-5036-3-4
%X PACS: 87.16.Tb, 87.85.RsThe voltage-dependent anion-selective channels are the most abundant proteins in the outer membrane of mitochondria [1,2]. VDACs are small (30-35 kDa) pore-forming proteins that are ubiquitous to all eukaryotes [3]. They are the major channels for the passage of ions and small molecules, including NADH and ATP across the mitochondrial outer membrane [4]. The regulation of the transport rates of these metabolites has been suggested to influence organellar and cellular metabolism, setting VDAC at a central position in the regulation of cellular energy metabolism. In humans, three different isoforms (hVDAC1, hVDAC2, hVDAC3) exist. They can be found in most tissues, albeit at different amounts [5,6]. VDAC exhibits numerous interactions with mitochondrial and cytosolic proteins [7,8] and even with components of the cytoskeleton [9,10]. Furthermore, VDAC has been reported to bind to pro- and anti-apoptotic proteins of the Bcl-2 family and has been proposed to be a major player in mitochondria mediated apoptosis, although its precise role is controversially discussed [11-15].A well-studied interaction is the binding of VDAC to the cytosolic protein hexokinase-I [16,17]. Hexokinase-I is highly expressed in brain, but is also prevalent in other tissues [16,18]. The binding of hexokinase-I to VDAC facilitates its access to ATP and it has been suggested that hexokinase-I modulates VDACs role in apoptosis [19,20].Notably, early studies on VDAC characterized this protein as the outer membrane hexokinase binding factor [21]. VDAC may enhance binding of hexokinase-I, but it is not essential for the binding of hexokinase-I to the outer membrane. Necessary and sufficient for mitochondrial binding of hexokinase-I is a 15 amino acid long N-terminal domain that inserts into the outer membrane [22].Biochemical data indicates that only VDAC1 but not VDAC2 binds hexokinase [23], although this finding was questioned by a different study [24]. Hence, currently, littl
%U http://www.biomedcentral.com/1757-5036/3/4