Delta Protein Kinase C Interacts with the d Subunit of the F1F0 ATPase in Neonatal Cardiac Myocytes Exposed to Hypoxia or Phorbol Ester

Nguyen, Tiffany M.; Ogbi, Mourad; Johnson, John A.

doi:10.1074/jbc.m801642200

Cited by 24 publications

(35 citation statements)

References 55 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…in mitochondrial homeostasis due to hypoxia for instance, the reduction of F 1 F o ATPase activity (35), which uses Pi to produce ATP, may lead to local levels of inorganic phosphate reaching even higher concentrations. Surviving hypoxic conditions is one of the main driving forces in the selection that leads to cancer progression.…”

Section: Discussionmentioning

confidence: 99%

Mitochondrial localization and structure-based phosphate activation mechanism of Glutaminase C with implications for cancer metabolism

Cassago

Ferreira

et al. 2012

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

233

288

View full text Add to dashboard Cite

Glutamine is an essential nutrient for cancer cell proliferation, especially in the context of citric acid cycle anaplerosis. In this manuscript we present results that collectively demonstrate that, of the three major mammalian glutaminases identified to date, the lesser studied splice variant of the gene gls, known as Glutaminase C (GAC), is important for tumor metabolism. We show that, although levels of both the kidney-type isoforms are elevated in tumor vs. normal tissues, GAC is distinctly mitochondrial. GAC is also most responsive to the activator inorganic phosphate, the content of which is supposedly higher in mitochondria subject to hypoxia. Analysis of X-ray crystal structures of GAC in different bound states suggests a mechanism that introduces the tetramerization-induced lifting of a "gating loop" as essential for the phosphate-dependent activation process. Surprisingly, phosphate binds inside the catalytic pocket rather than at the oligomerization interface. Phosphate also mediates substrate entry by competing with glutamate. A greater tendency to oligomerize differentiates GAC from its alternatively spliced isoform and the cycling of phosphate in and out of the active site distinguishes it from the liver-type isozyme, which is known to be less dependent on this ion.glutamine metabolism | Warburg effect

show abstract

Section: Discussionmentioning

confidence: 99%

Mitochondrial localization and structure-based phosphate activation mechanism of Glutaminase C with implications for cancer metabolism

Cassago

Ferreira

et al. 2012

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

233

288

View full text Add to dashboard Cite

show abstract

“…As glycolysis and mitochondrial oxidative phosphorylation are linked processes (Fantin et al, 2006), we tested if ErbB2-overexpressing cells, which possess a higher level of glycolysis, are less sensitive to inhibitors of oxidative phosphorylation. The MCF7 and MCF7/ErbB2 cells were treated with oligomycin, an ATPase inhibitor that specifically inhibits mitochondrial oxidative phosphorylation (Nguyen et al, 2008). In contrast to 2-DG and oxamate, oligomycin showed a stronger inhibitory effect on MCF7 cells compared to MCF7/ErbB2 cells (Figure 5c), suggesting that ErbB2-overexpressing cells may have a lower level of mitochondrial oxidative phosphorylation.…”

Section: Overexpression Of Erbb2 Increases the Sensitivity Of Breast mentioning

confidence: 99%

Upregulation of lactate dehydrogenase A by ErbB2 through heat shock factor 1 promotes breast cancer cell glycolysis and growth

et al. 2009

View full text Add to dashboard Cite

ErbB2 has been shown to activate signaling molecules that may regulate glucose metabolism. However, there is no evidence reported to directly link ErbB2 to glycolysis, and the mechanism underlying ErbB2-enhanced glycolysis is poorly understood. In this study, we investigated the role and mechanism of ErbB2 in regulating glycolysis. We found that ErbB2-overexpressing cells possessed a significantly higher level of glycolysis when compared to the ErbB2-low-expressing cells, and the downregulation of ErbB2 markedly decreased glycolysis. Overexpression of ErbB2 increased the expression of glycolysis-regulating molecules lactate dehydrogenase A (LDH-A) and heat shock factor 1 (HSF1). ErbB2 activated HSF1, indicated by the increased HSF1 trimer formation, and promoted HSF1 protein synthesis. HSF1 bound to LDH-A promoter and the downregulation of HSF1 reduced the expression of LDH-A and subsequently decreased cancer cell glycolysis and growth. Moreover, the glycolysis inhibitors, 2-deoxyglucose and oxamate, selectively inhibited the growth of ErbB2-overexpressing cells. Taken together, this study shows that in human breast cancer cells, ErbB2 promotes glycolysis at least partially through the HSF1-mediated upregulation of LDH-A. This pathway may have a major role in regulating glucose metabolism in breast cancer cells. These novel findings have important implications for the design of new approaches to target ErbB2-overexpressing breast cancers.

show abstract

“…PDGF-mediated tyrosine phosphorylation of the ␦-subunit of ATP synthase has also been reported in other cell types (9). F 0 F 1 -ATPase associates and interacts with protein kinase C ␦ (PKC-␦) in cardiac myocytes and with PKC-␤ in the hippocampus after transient ischemia (21,22). In vitro incubation of F 0 F 1 -ATPase with the recombinant PKC-␦ inhibits F 0 F 1 -ATPase activity (21).…”

mentioning

confidence: 99%

Protein Kinase C-α Interaction with F0F1-ATPase Promotes F0F1-ATPase Activity and Reduces Energy Deficits in Injured Renal Cells

Nowak

Bakajsova

2015

Journal of Biological Chemistry

View full text Add to dashboard Cite

Delta Protein Kinase C Interacts with the d Subunit of the F1F0 ATPase in Neonatal Cardiac Myocytes Exposed to Hypoxia or Phorbol Ester

Cited by 24 publications

References 55 publications

Mitochondrial localization and structure-based phosphate activation mechanism of Glutaminase C with implications for cancer metabolism

Mitochondrial localization and structure-based phosphate activation mechanism of Glutaminase C with implications for cancer metabolism

Upregulation of lactate dehydrogenase A by ErbB2 through heat shock factor 1 promotes breast cancer cell glycolysis and growth

Protein Kinase C-α Interaction with F0F1-ATPase Promotes F0F1-ATPase Activity and Reduces Energy Deficits in Injured Renal Cells

Contact Info

Product

Resources

About