title: Hexokinase inhibits flux of fluorescently labeled ATP through mitochondrial outer membrane porin.
abstract: Mitochondrial function requires maintaining metabolite fluxes across the mitochondrial outer membrane, which is mediated primarily by the voltage dependent anion channel (VDAC). We applied fluorescence correlation spectroscopy (FCS) to study regulation of the VDAC functional state by monitoring distribution of fluorescently labeled ATP (BODIPY-FL-ATP) in isolated intact rat liver and heart mitochondria. Addition of mitochondria to BODIPY-FL-ATP solution resulted in accumulation of the fluorescent probe in these organelles. The addition of hexokinase II (HKII) isolated from rat heart led to a decrease in the BODIPY-FL-ATP accumulation, while a 15-residue peptide corresponding to the N-terminal domain of hexokinase did not produce this effect. Therefore, the hexokinase-induced inhibition of the ATP flow mediated by VDAC was revealed in isolated mitochondria.
authors.affiliation: Belozersky Institute of Physico-Chemical Biology, Department of Bioengineering and Bioinformatics, Moscow State University, Moscow, Russia.
authors.forename: Irina V
authors.initials: IV
authors.lastname: Perevoshchikova
authors.forename: Savva D
authors.initials: SD
authors.lastname: Zorov
authors.forename: Elena A
authors.initials: EA
authors.lastname: Kotova
authors.forename: Dmitry B
authors.initials: DB
authors.lastname: Zorov
authors.forename: Yuri N
authors.initials: YN
authors.lastname: Antonenko
mesh_terms: D000818:Animals; D006593:Hexokinase / Q000378:metabolism*; D008928:Mitochondria / Q000378:metabolism*; D051336:Mitochondrial Membranes / Q000378:metabolism*; D018272:Porins / Q000737:chemistry / Q000378:metabolism*; D051381:Rats; D050995:Voltage-Dependent Anion Channel 1 / Q000378:metabolism; D050994:Voltage-Dependent Anion Channels / Q000378:metabolism*
chemical_list: D018272:Porins; C494764:Vdac1 protein, rat; D050994:Voltage-Dependent Anion Channels; D050995:Voltage-Dependent Anion Channel 1; D006593:Hexokinase