A new level of regulation in gluconeogenesis: metabolic state modulates the intracellular localization of aldolase B and its interaction with liver fructose-1,6-bisphosphatase

Droppelmann, Cristian A.; Sáez, Doris E.; Asenjo, Joel L.; Yáñez, Alejandro J.; Garcı́a-Rocha, Mar; Concha, Ilona I.; Grez, Manuel; Guinovart, Joan J.; Slebe, Juan C.

doi:10.1042/bj20150269

Cited by 18 publications

(18 citation statements)

References 68 publications

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“…A specific and regulated interaction between ALDOB and the rate-limiting gluconeogenic enzyme fructose-1, 6-bisphosphatase 1 (FBP1) has been shown. This result confirms the view that ALDOA and ALDOB play different roles in glucose metabolism [22]. The shut-down of the gluconeogenic pathway was thus one of the most relevant metabolic changes observed and can be regarded as a metabolic hallmark in pRCC.…”

Section: Resultssupporting

confidence: 87%

Papillary Renal Cell Carcinomas Rewire Glutathione Metabolism and Are Deficient in Both Anabolic Glucose Synthesis and Oxidative Phosphorylation

Ahmad

Paffrath

Clima

et al. 2019

Cancers

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Papillary renal cell carcinoma (pRCC) is a malignant kidney cancer with a prevalence of 7–20% of all renal tumors. Proteome and metabolome profiles of 19 pRCC and patient-matched healthy kidney controls were used to elucidate the regulation of metabolic pathways and the underlying molecular mechanisms. Glutathione (GSH), a main reactive oxygen species (ROS) scavenger, was highly increased and can be regarded as a new hallmark in this malignancy. Isotope tracing of pRCC derived cell lines revealed an increased de novo synthesis rate of GSH, based on glutamine consumption. Furthermore, profound downregulation of gluconeogenesis and oxidative phosphorylation was observed at the protein level. In contrast, analysis of the The Cancer Genome Atlas (TCGA) papillary RCC cohort revealed no significant change in transcripts encoding oxidative phosphorylation compared to normal kidney tissue, highlighting the importance of proteomic profiling. The molecular characteristics of pRCC are increased GSH synthesis to cope with ROS stress, deficient anabolic glucose synthesis, and compromised oxidative phosphorylation, which could potentially be exploited in innovative anti-cancer strategies.

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Section: Resultssupporting

confidence: 87%

Papillary Renal Cell Carcinomas Rewire Glutathione Metabolism and Are Deficient in Both Anabolic Glucose Synthesis and Oxidative Phosphorylation

Ahmad

Paffrath

Clima

et al. 2019

Cancers

View full text Add to dashboard Cite

show abstract

“…A specific and regulated interaction between ALDOB and the rate-limiting gluconeogenic enzyme fructose-1, 6-bisphosphatase 1 (FBP1) has been shown. This result confirms the view that ALDOA and ALDOB play different roles in glucose metabolism (21). The shut-down of the gluconeogenic pathway was thus one of the most relevant metabolic changes observed and can be regarded as a metabolic hallmark in pRCC.…”

Section: Anabolic Glucose Synthesis Was Abated In Prccsupporting

confidence: 87%

Papillary renal cell carcinomas rewire glutathione metabolism and are deficient in anabolic glucose synthesis

Alahmad

Paffrath

Clima

et al. 2019

Preprint

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Papillary renal cell carcinoma (pRCC) is a malignant kidney cancer with a prevalence of 7-20% of all renal tumors. Proteome and metabolome profiles of 19 pRCC and patient-matched healthy kidney controls were used to elucidate the regulation of metabolic pathways and the underlying molecular mechanisms. Glutathione (GSH), a main reactive oxygen species (ROS) scavenger, was highly increased and can be regarded as a new hallmark in this malignancy. Isotope tracing of pRCC derived cell lines revealed an increased de novo synthesis rate of GSH, based on glutamine consumption. Furthermore, rewiring of the main pathways involved in ATP and glucose synthesis was observed at the protein level. In contrast, transcripts encoding for the respiratory chain were not regulated, which prompts for non-genetic profiling. The molecular characteristics of pRCC are increased GSH synthesis to cope with ROS stress, deficient anabolic glucose synthesis, and compromised oxidative phosphorylation, which could potentially be exploited in innovative anti-cancer strategies.

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“…Transcriptomics indicates that aldolase B mRNA is also highly upregulated in rat islets cultured at high glucose 40 and in β-cells of T2D subjects 42,43 , where it correlates positively with HbA1c and negatively with insulin release 43 . In hepatocytes, aldolase A mainly participates in glycolysis, whereas aldolase B is principally involved in gluconeogenesis 44 . If this is also true in β-cells, it would favour glycogen production.…”

Section: Discussionmentioning

confidence: 99%

Diabetes causes marked inhibition of mitochondrial metabolism in pancreatic β-cells

et al. 2019

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Diabetes is a global health problem caused primarily by the inability of pancreatic β-cells to secrete adequate levels of insulin. The molecular mechanisms underlying the progressive failure of β-cells to respond to glucose in type-2 diabetes remain unresolved. Using a combination of transcriptomics and proteomics, we find significant dysregulation of major metabolic pathways in islets of diabetic βV59M mice, a non-obese, eulipidaemic diabetes model. Multiple genes/proteins involved in glycolysis/gluconeogenesis are upregulated, whereas those involved in oxidative phosphorylation are downregulated. In isolated islets, glucose-induced increases in NADH and ATP are impaired and both oxidative and glycolytic glucose metabolism are reduced. INS-1 β-cells cultured chronically at high glucose show similar changes in protein expression and reduced glucose-stimulated oxygen consumption: targeted metabolomics reveals impaired metabolism. These data indicate hyperglycaemia induces metabolic changes in β-cells that markedly reduce mitochondrial metabolism and ATP synthesis. We propose this underlies the progressive failure of β-cells in diabetes.

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A new level of regulation in gluconeogenesis: metabolic state modulates the intracellular localization of aldolase B and its interaction with liver fructose-1,6-bisphosphatase

Abstract: We have demonstrated that cellular localization of aldolase B and its interaction with fructose-1,6-bisphosphatase-1 (FBPase-1) is modulated by the metabolic conditions. These results show a new level of regulation for aldolase B and FBPase-1 in a cellular context.

Cited by 18 publications

References 68 publications

Papillary Renal Cell Carcinomas Rewire Glutathione Metabolism and Are Deficient in Both Anabolic Glucose Synthesis and Oxidative Phosphorylation

Papillary Renal Cell Carcinomas Rewire Glutathione Metabolism and Are Deficient in Both Anabolic Glucose Synthesis and Oxidative Phosphorylation

Papillary renal cell carcinomas rewire glutathione metabolism and are deficient in anabolic glucose synthesis

Diabetes causes marked inhibition of mitochondrial metabolism in pancreatic β-cells

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