The mitochondrial outer membrane channel, VDAC, is modulated by a soluble protein

Holden, Marcia J.; Colombini, Marco

doi:10.1016/0014-5793(88)81040-8

Cited by 83 publications

(25 citation statements)

References 18 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…azepine receptor, mtHSP70, ORDIC channel, and ANT (reviewed in [5][6][7]). VDAC interacts with a specific unidentified modulator, possibly in the intermembrane space, which increases its voltage dependence and decreases its conductance [126,127]. VDAC also interacts with apoptosis regulating proteins, mainly members of the Bcl-2 family [91,108,128], glyceraldehyde 3-phosphate dehydrogenase [7] and gelsolin [90], which are considered to be pro-apoptotic proteins [129,130].…”

Section: Protein Modulatorsmentioning

confidence: 98%

The Voltage-Dependent Anion Channel (VDAC): Function in Intracellular Signalling, Cell Life and Cell Death

Shoshan‐Barmatz

Israelson²,

Brdiczka³

et al. 2006

CPD

286

329

View full text Add to dashboard Cite

Research over the last decade has extended the prevailing view of mitochondria to include functions well beyond the critical bioenergetics role in supplying ATP. It is now recognized that mitochondria play a crucial role in cell signaling events, inter-organelle communication, aging, many diseases, cell proliferation and cell death. Apoptotic signal transmission to the mitochondria results in the efflux of a number of potential apoptotic regulators to the cytosol that trigger caspase activation and lead to cell destruction. Accumulating evidence indicates that the voltage-dependent anion channel (VDAC) is involved in this release of proteins via the outer mitochondrial membrane. VDAC in the outer mitochondrial membrane is in a crucial position in the cell, forming the main interface between the mitochondrial and the cellular metabolisms. VDAC has been recognized as a key protein in mitochondria-mediated apoptosis since it is the proposed target for the pro- and anti-apoptotic Bcl2-family of proteins and due to its function in the release of apoptotic proteins located in the inter-membranal space. The diameter of the VDAC pore is only about 2.6-3 nm, which is insufficient for passage of a folded protein like cytochrome c. New work suggests pore formation by homo-oligomers of VDAC or hetero-oligomers composed of VDAC and pro-apoptotic proteins such as Bax or Bak. This review provides insights into the central role of VDAC in cell life and death and emphasizes its function in the regulation of mitochondria-mediated apoptosis and, thereby, its potential as a rational target for new therapeutics.

show abstract

Section: Protein Modulatorsmentioning

confidence: 98%

The Voltage-Dependent Anion Channel (VDAC): Function in Intracellular Signalling, Cell Life and Cell Death

Shoshan‐Barmatz

Israelson²,

Brdiczka³

et al. 2006

CPD

286

329

View full text Add to dashboard Cite

show abstract

“…The existence of genetically distinct porins and of multiple isoforms has been proposed (31). Porin at mitochondrial contact sites switches ion selectivity after a soluble protein induces a conformational change (32). Ion selectivity of the pore also depends on the inner mitochondrial membrane potential (33).…”

Section: Discussionmentioning

confidence: 99%

Targeting of hexokinase 1 to liver and hepatoma mitochondria.

Gelb

Adams

Jones

et al. 1992

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

The proportion of hexokinase (HK; EC 2.7.1.1) isozyme 1 (HK1) that is bound to the outer mitochondrial membrane is tissue specific and developmentally regulated. HK activity is known to be markedly elevated in many cancer cells and a significant fraction is mitochondrial bound.This study examined the role of the 15-amino acid N-terminal domain ofHK1 in binding to liver and hepatoma mitochondria. A chimeric reporter construct, pCMVHKCAT, encoding this HK1 domain coupled to the chloramphenicol acetyltransferase (CAT) gene was electroporated into mouse Hepa 1-6 hepatoma cells. After digitonin treatment, cell fractions were assayed for HK, lactate dehydrogenase, and CAT activities. Digitonin (75 ,ug/mg of protein) caused cytosolic leak but 70% of HK remained with the pellet. HKCAT, like HK, remained predominantly with the pellet; CAT from the control, pCMVCAT, remained mostly unbound. Binding of membrane-free cell extracts to rat liver mitochondria in vitro showed 91% of the HKCAT bound, whereas only 12% of CAT bound. Specificity of HKCAT binding to mitochondria was demonstrated by competition of HK1 for HKCAT binding sites on rat liver mitochondria as well as by blockage of HKCAT binding by N,N'-dicyclohexylcarbodiimide, which covalently binds to porin and blocks HK1 binding. Deletional mutant constructs of HKCAT showed reduced binding with increasing deletion size. In summary, these studies demonstrate that the 15-amino acid N-terminal domain of HK1 is necessary and sufficient to confer mitochondrial binding properties to CAT and that there is specificity for this binding to the mitochondria. Hexokinase (HK; EC 2.7.1.1) catalyzes the phosphorylation of glucose to glucose 6-phosphate, an ATP-dependent reaction that serves as the entry point for glucose into glycolysis and the hexose-monophosphate shunt. Four isozymes of HK are present in mammalian tissues. HK1, like HK2 and HK3, contains a catalytic domain in the carboxyl half of the protein and a regulatory domain in the amino half. Sequence data for HK1 cDNA from several species demonstrate substantial homology between the two halves as well as an additional 15-amino acid domain at the N terminus that is completely conserved between rat brain, human kidney, and bovine heart HK1 (1-3).

show abstract

“…Analogous channels are also in the fungus, Neurospora crassa (Colombini, 1980;Mannella, Colombini & Frank, 1983), and can be modulated by a soluble mitochondrial protein (Holden & Colombini, 1989). As with animal VDACs, the plant channels are weakly anion selective, have a large single channel G (about 3-9 nS in 1 M KCI) and close as the PD across the membrane moves from 0 mV.…”

Section: Channels In Mitochondriamentioning

confidence: 99%

Tansley Review No. 21 Plant ion channels: whole‐cell and single channel studies

Tester¹

1990

New Phytologist

301

166

View full text Add to dashboard Cite

SUMMARY Ion channels are proteins which catalyse rapid, passive, electrogenic uniport of ions through pores spanning an otherwise poorly permeable lipid bilayer. Among other processes, fluxes through ion channels are responsible for action potentials – large, transient changes in membrane potential which have been known of in plants for over 100 years. Much disparate information on ion channels in plant cells has accumulated over the past few years. In an attempt to synthesize these data, the properties of at least 18 different ion channels are collated in this review. Channels are initially classified according to ion selectivity (Ca2+, Cl−, K+ and H+); then gating characteristics (i.e. control of opening and closing), unitary conductance and pharmacology are used to distinguish further different sub‐types of channels. To provide a background for this overview, the fundamental properties which define ion channels in animal cells, namely conduction, selectivity and gating, are described. Appropriate techniques for the study of ion channels are also assessed. The review concludes with a discussion on the role of ion channels in plant cells, although any comment on functions beyond turgor regulation and general statements about signalling remains largely speculative. The study of ion channels in plant cells is still at an early stage and it is hoped that this review will provide a framework upon which further work in both algae and vascular plants can be based.

show abstract

The mitochondrial outer membrane channel, VDAC, is modulated by a soluble protein

Cited by 83 publications

References 18 publications

The Voltage-Dependent Anion Channel (VDAC): Function in Intracellular Signalling, Cell Life and Cell Death

The Voltage-Dependent Anion Channel (VDAC): Function in Intracellular Signalling, Cell Life and Cell Death

Targeting of hexokinase 1 to liver and hepatoma mitochondria.

Tansley Review No. 21 Plant ion channels: whole‐cell and single channel studies

Contact Info

Product

Resources

About