Hexokinase-binding properties of the mitochondrial VDAC protein: Inhibition by DCCD and location of putative DCCD-binding sites

Nakashima, Richard A.

doi:10.1007/bf00762518

Cited by 39 publications

(28 citation statements)

References 45 publications

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“…Hexokinase II binds to the VDAC on the outer mitochondrial membrane (Nakashima, 1989;Wilson, 2003). Sirtuin-3 is localized to the mitochondrial matrix, indicating that its modulation of hexokinase II binding must be indirect.…”

Section: Sirtuin-3 Deacetylates and Inactivates Cyclophilin Dmentioning

confidence: 99%

Sirtuin-3 deacetylation of cyclophilin D induces dissociation of hexokinase II from the mitochondria

Shulga

Wilson-Smith

Pastorino

2010

Journal of Cell Science

153

126

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We demonstrate that the transition from a reliance on glycolysis to oxidative phosphorylation in a transformed cell line is dependent on an increase in the levels and activity of sirtuin-3. Sirtuin-3 deacetylates cyclophilin D, diminishing its peptidyl-prolyl cis-trans isomerase activity and inducing its dissociation from the adenine nucleotide translocator. Moreover, the sirtuin-3-induced inactivation of cyclophilin D causes a detachment of hexokinase II from the mitochondria that is necessary for stimulation of oxidative phosphorylation. These results might have important implications for the role of sirtuin-3 in the metabolism of some cancer cells and their susceptibility to mitochondrial injury and cytotoxicity.

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Section: Sirtuin-3 Deacetylates and Inactivates Cyclophilin Dmentioning

confidence: 99%

Sirtuin-3 deacetylation of cyclophilin D induces dissociation of hexokinase II from the mitochondria

Shulga

Wilson-Smith

Pastorino

2010

Journal of Cell Science

153

126

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“…The VDAC is the core component of the permeability transition pore and acts as a gatekeeper of solute movement between mitochondria and the cytosol (52,53). SUS interaction with VDAC may be analogous to hexokinase interaction with the latter in animal cells (54,55). Hexokinase is associated with mitochondria (although extrinsically) via its interaction with VDAC in a tissue-specific, isoform-dependent, and metabolically regulated manner.…”

Section: Sus Is An Integral Protein Of Maize Mitochondria-mentioning

confidence: 99%

“…Hexokinase is associated with mitochondria (although extrinsically) via its interaction with VDAC in a tissue-specific, isoform-dependent, and metabolically regulated manner. This specific localization of hexokinase seems to enable a tight coupling between glycolysis and oxidative phosphorylation as well as to regulate the opening of mitochondrial permeability transition pore, nutrient/sugar signaling, and apoptosis (54,55).…”

Section: Sus Is An Integral Protein Of Maize Mitochondria-mentioning

confidence: 99%

Mitochondrial Localization and Putative Signaling Function of Sucrose Synthase in Maize

Subbaiah

Palaniappan

Duncan

et al. 2006

Journal of Biological Chemistry

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In many organisms, an increasing number of proteins seem to play two or more unrelated roles. Here we report that maize sucrose synthase (SUS) is distributed in organelles not involved in sucrose metabolism and may have novel roles beyond sucrose degradation. Bioinformatics analysis predicts that among the three maize SUS isoforms, SH1 protein has a putative mitochondrial targeting peptide (mTP). We validated this prediction by the immunodetection of SUS in mitochondria. Analysis with isoform-specific antisera revealed that both SH1 and SUS1 are represented in mitochondria, although the latter lacks a canonical mTP. The SUS2 isoform is not detectable in mitochondria, despite its presence in the cytosol. In maize primary roots, the mitochondrion-associated SUS (mtSUS; which includes SH1 and SUS1) is present mostly in the root tip, indicating tissue-specific regulation of SUS compartmentation. Unlike the glycolytic enzymes that occur attached to the outside of mitochondria, SH1 and SUS1 are intramitochondrial. The low abundance of SUS in mitochondria, its high K m value for sucrose, and the lack of sucrose in mitochondria suggest that mtSUS plays a non-sucrolytic role. Co-immunoprecipitation studies indicate that SUS interacts with the voltage-dependent anion channel in an isoform-specific and anoxia-enhanced manner and may be involved in the regulation of solute fluxes into and out of mitochondria. In several plant species, at least one of the SUS proteins possesses a putative mTP, indicating the conservation of the noncatalytic function across plant species. Taken together, these observations suggest that SUS has a novel noncatalytic function in plant cells.In both plant and animal cells, a small number of catalytic and structural proteins play additional roles that in some cases are regulatory in nature (1-3). These "moonlighting" proteins possess the ability to assemble into multiprotein complexes and mediate sophisticated biological functions such as integrating signals. Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) 2 is the most studied among such versatile proteins (4). Besides its pivotal role in energy metabolism, GAPDH is shown to be involved in membrane fusion, microtubule assembly, RNA transport, DNA replication and repair, and cell death (5). The functional diversity of GAPDH is facilitated by its ability to interact with other proteins and translocate to multiple subcellular compartments. Sucrose synthase (SUS) catalyzes the reversible conversion of sucrose and UDP into fructose and UDP-glucose and is a key player in plant sucrose catabolism. In maize, the following three genes encoding sucrose synthase are known: sus1, sus2, and sh1. The isoforms encoded by these genes are symbolized SUS1, SUS2, and SUS-SH1, respectively (6). In this study, for the sake of simplicity, we call the SUS-SH1 isoform SH1. All the three isoforms are predominantly recovered as soluble (cytosolic) proteins from plant cells, in accordance with their predicted secondary structures. The well documented function of this en...

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“…They represent the binding sites for several cytosolic enzymes, including the isoforms of hexokinase and glycerol kinase [1,2]. VDACs have recently been shown to conduct ATP and providing a possible mechanism for the regulation of adenine nucleotide flux [3].…”

Section: Introductionmentioning

confidence: 99%

Changes of voltage-dependent anion-selective channel proteins VDAC1 and VDAC2 brain levels in patients with Alzheimer's disease and Down Syndrome

Yoo¹,

Fountoulakis²,

Cairns³

et al. 2001

Electrophoresis

130

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Voltage-dependent anion-selective channel proteins (VDACs) are pore-forming proteins found in the other mitochondrial membrane of all eukaryotes and in brain postsynaptic membranes. VDACs regulate anion fluxes of a series of metabolites including ATP, thus regulating mitochondrial metabolic functions. We determined protein levels of VDACs in individual post-mortem brain regions of patients with Down Syndrome (DS) and Alzheimer's disease (AD) using two-dimensional electrophoresis (2-DE) and matrix-assisted laser desorption/ionization-mass spectroscopy (MALDI-MS). VDAC1 (SWISS-PROT accession number P21796) and VDAC2 (P45880) were unambiguously identified and quantified, but VDAC3 was not found. The spots representing VDAC1 were separated with different p/s (p/7.5, 8.5, and 10.0) probably caused by post-translational modifications as, e.g., phosphorylation. In DS cerebellum, total VDAC1 protein was elevated significantly whereas VDAC2 did not show any significant alterations. In AD brains, VDAC1 p/10.0 was significantly reduced in temporal, frontal, and occipital cortex with the p/7.5 form elevated in occipital cortex. Total VDAC1 was significantly decreased in frontal cortex and thalamus. VDAC2 was significantly elevated in temporal cortex only. The biological meaning of our results may be derangement of voltage-dependent anion-selective channel function and reflecting impaired glucose, energy, and intermediary metabolism as well as apoptotic mechanisms.

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Hexokinase-binding properties of the mitochondrial VDAC protein: Inhibition by DCCD and location of putative DCCD-binding sites

Cited by 39 publications

References 45 publications

Sirtuin-3 deacetylation of cyclophilin D induces dissociation of hexokinase II from the mitochondria

Sirtuin-3 deacetylation of cyclophilin D induces dissociation of hexokinase II from the mitochondria

Mitochondrial Localization and Putative Signaling Function of Sucrose Synthase in Maize

Changes of voltage-dependent anion-selective channel proteins VDAC1 and VDAC2 brain levels in patients with Alzheimer's disease and Down Syndrome

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