Porin interaction with hexokinase and glycerol kinase: Metabolic microcompartmentation at the outer mitochondrial membrane

Adams, Volker; Griffin, Lisa; Towbin, Jeffrey A.; Gelb, Bruce D.; Worley, Kim C.; McCabe, Edward R.B.

doi:10.1016/0885-4505(91)90032-g

Cited by 134 publications

(65 citation statements)

References 147 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These mechanisms are based on the participation of plasmin reductases [Stathakis et al, 1999], one of which has been identified as the glycolytic enzyme phosphoglycerate kinase (PGK) [Lay et al, 2000a]. PGK is an outer mitochondrial membrane protein that is usually associated with VDAC1 [Adams et al, 1991]. Therefore, binding of plasminogen via K5 to VDAC1 is followed by its conversion to Pm by its physiologic activators, urokinase (u-PA) or tissue-type (t-PA) plasminogen activators.…”

Section: Kringle 5 Also Has Anti-angiogenic Activitymentioning

confidence: 99%

Angiostatin's molecular mechanism: Aspects of specificity and regulation elucidated

Wahl

Kenan

Gonzalez-Gronow

et al. 2005

J of Cellular Biochemistry

114

View full text Add to dashboard Cite

Tumor growth requires the development of new vessels that sprout from pre-existing normal vessels in a process known as ''angiogenesis'' [Folkman (1971) N Engl J Med 285:1182-1186. These new vessels arise from local capillaries, arteries, and veins in response to the release of soluble growth factors from the tumor mass, enabling these tumors to grow beyond the diffusion-limited size of approximately 2 mm diameter. Angiostatin, a naturally occurring inhibitor of angiogenesis, was discovered based on its ability to block tumor growth in vivo by inhibiting the formation of new tumor blood vessels [O'Reilly et al. (1994a) Cold Spring Harb Symp Quant Biol 59:471-482]. Angiostatin is a proteolytically derived internal fragment of plasminogen and may contain various members of the five plasminogen ''kringle'' domains, depending on the exact sites of proteolysis. Different forms of angiostatin have measurably different activities, suggesting that much remains to be elucidated about angiostatin biology. A number of groups have sought to identify the native cell surface binding site(s) for angiostatin, resulting in at least five different binding sites proposed for angiostatin on the surface of endothelial cells (EC). This review will consider the data supporting all of the various reported angiostatin binding sites and will focus particular attention on the angiostatin binding protein identified by our group: F 1 F O ATP synthase. There have been several developments in the quest to elucidate the mechanism of action of angiostatin and the regulation of its receptor. The purpose of this review is to describe the highlights of research on the mechanism of action of angiostatin, its' interaction with ATP synthase on the EC surface, modulators of its activity, and issues that should be explored in future research related to angiostatin and other anti-angiogenic agents.

show abstract

Section: Kringle 5 Also Has Anti-angiogenic Activitymentioning

confidence: 99%

Angiostatin's molecular mechanism: Aspects of specificity and regulation elucidated

Wahl

Kenan

Gonzalez-Gronow

et al. 2005

J of Cellular Biochemistry

114

View full text Add to dashboard Cite

show abstract

“…For NC-HK from maize and rice, it is suggested a stronger hydrophobic character and this property may be potentially important to promote a tight association between HK and mitochondria in maize. The rat brain HK possesses a site of cleavage for chymotrypsin on its hydrophobic N-terminal (20,21,23,24,27,38). Mild chymotrypsin digestion effectively removes the N-terminal from rat HK, preventing the enzyme from associating with mitochondria or adhering to the phenyl-Sepharose column (27).…”

Section: Effect Of Limited Chymotrypsin Hydrolysis On Hydrophobic Intmentioning

confidence: 99%

“…It has been suggested that in castor bean (Ricinus communis) HK and mitochondria interact in a way similar to that described for rat brain (6,20). In the rat brain, HK is associated with mitochondria through the porin protein, also called voltage-dependent anion channel (21). The rat HK dissociates from the mitochondrial porin in a reversible manner depending on the levels of glucose-6-phosphate (22)(23)(24).…”

Section: Introductionmentioning

confidence: 99%

Partial purification of tightly bound mitochondrial hexokinase from maize (Zea mays L.) root membranes

Rezende

Logullo

Meyer

et al. 2006

Braz J Med Biol Res

View full text Add to dashboard Cite

In mammals, hexokinase (HK) is strategically located at the outer membrane of mitochondria bound to the porin protein. The mitochondrial HK is a crucial modulator of apoptosis and reactive oxygen species generation. In plants, these properties related to HK are unknown. In order to better understand the physiological role of non-cytosolic hexokinase (NC-HK) in plants, we developed a purification strategy here described. Crude extract of 400 g of maize roots (230 mg protein) contained a specific activity of 0.042 µmol G6P min -1 mg PTN -1 . After solubilization with detergent two fractions were obtained by DEAE column chromatography, NC-HK 1 (specific activity = 3.6 µmol G6P min -1 mg PTN -1 and protein recovered = 0.7 mg) and NC-HK 2. A major purification (yield = 500-fold) was obtained after passage of NC-HK 1 through the hydrophobic phenyl-Sepharose column. The total amount of protein and activity recovered were 0.04 and 18%, respectively. The NC-HK 1 binds to the hydrophobic phenyl-Sepharose matrix, as observed for rat brain HK. Mild chymotrypsin digestion did not affect adsorption of NC-HK 1 to the hydrophobic column as it does for rat HK I. In contrast to mammal mitochondrial HK, glucose-6-phosphate, clotrimazole or thiopental did not dissociate NC-HK from maize (Zea mays) or rice (Oryza sativa) mitochondrial membranes. These data show that the interaction between maize or rice NC-HK to mitochondria differs from that reported in mammals, where the mitochondrial enzyme can be displaced by modulators or pharmacological agents known to interfere with the enzyme binding properties with the mitochondrial porin protein. Correspondence

show abstract

“…cerol kinase, are bound to the outer surface of the mitochondrion by interaction with porin [7]. The biological relevance of the mitochondrial localization of the kinases has been proposed as an advantage in supplying these enzymes with mitochondrially formed ATP and by analogy supplying oxidative phosphorylation with ADP generated by kinase activity [8,9].…”

Section: Pi1s0014-5793(96)00455-3mentioning

confidence: 99%

“…In the mitochondrial periphery, several kinases are present [6,7]. These include adenylate kinase and creatine kinase which are localized between the two envelope membranes.…”

Section: Introductionmentioning

confidence: 99%

ADP delivery from adenylate kinase in the mitochondrial intermembrane space to oxidative phosphorylation increases in the presence of macromolecules

1996

View full text Add to dashboard Cite

Macromolecules were added to isolated rat fiver mitochondria to mimic cytosofic macromolecules and tested for their effects on the ADP delivery from adenylate kinase in the intermembrane space to oxidative phosphorylation. In the presence of 10% (w/v) dextran M20 or bovine serum albumin, approximately 60% of the maximal ADP flux from adenylate kinase to oxidative phosphorylation was not accessible to an extramitochondrial ADP scavenger. In the absence of macromolecules this was 34%. ADP determinations from incubations with macromolecules demonstrated the existence of fluxdependent ADP concentration gradients across the outer membrane which can be as high as 12 tiM.

show abstract

Porin interaction with hexokinase and glycerol kinase: Metabolic microcompartmentation at the outer mitochondrial membrane

Cited by 134 publications

References 147 publications

Angiostatin's molecular mechanism: Aspects of specificity and regulation elucidated

Angiostatin's molecular mechanism: Aspects of specificity and regulation elucidated

Partial purification of tightly bound mitochondrial hexokinase from maize (Zea mays L.) root membranes

ADP delivery from adenylate kinase in the mitochondrial intermembrane space to oxidative phosphorylation increases in the presence of macromolecules

Contact Info

Product

Resources

About