Techniques to Monitor Glycolysis

TeSlaa, Tara; Teitell, Michael A.

doi:10.1016/b978-0-12-416618-9.00005-4

Cited by 233 publications

(196 citation statements)

References 48 publications

(56 reference statements)

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“…Qualitative analysis of glycolysis determined by the extracellular acidification rate (ECAR) was markedly repressed in DKO platelets (Figure 1E). Of note, ECAR was not zero in DKO platelets potentially reflecting acidification of the media, by acids other than lactate (TeSlaa and Teitell, 2014). Consistent with studies in human platelets (Karpatkin, 1968), thrombin increased glycolysis by ~2-fold in control murine platelets.…”

Section: Resultsmentioning

confidence: 99%

Deletion of GLUT1 and GLUT3 Reveals Multiple Roles for Glucose Metabolism in Platelet and Megakaryocyte Function

et al. 2017

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Summary Anucleate platelets circulate in the blood to facilitate thrombosis and diverse immune functions. Platelet activation leading to clot formation correlates with increased glycogenolysis, glucose uptake, glucose oxidation, and lactic acid production. Simultaneous deletion of glucose transporter (GLUT) 1 and GLUT3 (double knockout (DKO)) specifically in platelets completely abolished glucose uptake. In DKO platelets mitochondrial oxidative metabolism of non-glycolytic substrates such as glutamate, increased. Thrombosis and platelet activation were decreased through impairment at multiple activation nodes including Ca2+ signaling, degranulation, and integrin activation. DKO mice developed thrombocytopenia, secondary to impaired pro-platelet formation from megakaryocytes, and increased platelet clearance resulting from cytosolic calcium overload and calpain activation. Systemic treatment with oligomycin, inhibiting mitochondrial metabolism, induced rapid clearance of platelets with circulating counts dropping to zero in DKO but not wildtype mice, demonstrating an essential role for energy metabolism in platelet viability. Thus substrate metabolism is essential for platelet production, activation and survival.

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Section: Resultsmentioning

confidence: 99%

Deletion of GLUT1 and GLUT3 Reveals Multiple Roles for Glucose Metabolism in Platelet and Megakaryocyte Function

et al. 2017

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“…S5D, E). Extracellular flux analysis measures the rate of acidification of the medium and is an indicator of glycolytic flux [51]. We observed that TNBC cells have higher extracellular flux (ECAR) indicative of higher glycolysis (Fig.…”

Section: Resultsmentioning

confidence: 99%

Aggressive triple negative breast cancers have unique molecular signature on the basis of mitochondrial genetic and functional defects

Guha¹,

Srinivasan²,

Raman³

et al. 2018

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Diseas

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Metastatic breast cancer is a leading cause of cancer-related deaths in women worldwide. Patients with triple negative breast cancer (TNBCs), a highly aggressive tumor subtype, have a particularly poor prognosis. Multiple reports demonstrate that altered content of the multicopy mitochondrial genome (mtDNA) in primary breast tumors correlates with poor prognosis. We earlier reported that mtDNA copy number reduction in breast cancer cell lines induces an epithelial-mesenchymal transition associated with metastasis. However, it is unknown whether the breast tumor subtypes (TNBC, Luminal and HER2+) differ in the nature and amount of mitochondrial defects and if mitochondrial defects can be used as a marker to identify tumors at risk for metastasis. By analyzing human primary tumors, cell lines and the TCGA dataset, we demonstrate a high degree of variability in mitochondrial defects among the tumor subtypes and TNBCs, in particular, exhibit higher frequency of mitochondrial defects, including reduced mtDNA content, mtDNA sequence imbalance (mtRNR1:ND4), impaired mitochondrial respiration and metabolic switch to glycolysis which is associated with tumorigenicity. We identified that genes involved in maintenance of mitochondrial structural and functional integrity are differentially expressed in TNBCs compared to non-TNBC tumors. Furthermore, we identified a subset of TNBC tumors that contain lower expression of epithelial splicing regulatory protein (ESRP)-1, typical of metastasizing cells. The overall impact of our findings reported here is that mitochondrial heterogeneity among TNBCs can be used to identify TNBC patients at risk of metastasis and the altered metabolism and metabolic genes can be targeted to improve chemotherapeutic response.

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“…Ϫ/Ϫ adipocytes exhibited elevated nonglycolytic acidification (ECAR after 2-deoxyglucose [2-DG] treatment) produced by the acidification of CO 2 , the end product of the tricarboxylic acid cycle (47). The addition of glucose increased ECAR in Bscl2 ϩ/ϩ brown adipocytes, and more so in cells deficient in Bscl2, suggesting a greater ability to increase glycolysis.…”

Section: Bscl2mentioning

confidence: 99%

Berardinelli-Seip Congenital Lipodystrophy 2/Seipin Is Not Required for Brown Adipogenesis but Regulates Brown Adipose Tissue Development and Function

Zhou

Black

Benson

et al. 2016

Molecular and Cellular Biology

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Brown adipose tissue (BAT) plays a unique role in regulating whole-body energy homeostasis by dissipating energy through thermogenic uncoupling. Berardinelli-Seip congenital lipodystrophy (BSCL) type 2 (BSCL2; also known as seipin) is a lipodystrophy-associated endoplasmic reticulum membrane protein essential for white adipocyte differentiation. Whether BSCL2 directly participates in brown adipocyte differentiation, development, and function, however, is unknown. We show that BSCL2 expression is increased during brown adipocyte differentiation. Its deletion does not impair the classic brown adipogenic program but rather induces premature activation of differentiating brown adipocytes through cyclic AMP (cAMP)/protein kinase A (PKA)-mediated lipolysis and fatty acid and glucose oxidation, as well as uncoupling. cAMP/PKA signaling is physiologically activated during neonatal BAT development in wild-type mice and greatly potentiated in mice with genetic deletion of Bscl2 in brown progenitor cells, leading to reduced BAT mass and lipid content during neonatal brown fat formation. However, prolonged overactivation of cAMP/PKA signaling during BAT development ultimately causes apoptosis of brown adipocytes through inflammation, resulting in BAT atrophy and increased overall adiposity in adult mice. These findings reveal a key cellautonomous role for BSCL2 in controlling BAT mass/activity and provide novel insights into therapeutic strategies targeting cAMP/PKA signaling to regulate brown adipocyte function, viability, and metabolic homeostasis.

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Techniques to Monitor Glycolysis

Cited by 233 publications

References 48 publications

Deletion of GLUT1 and GLUT3 Reveals Multiple Roles for Glucose Metabolism in Platelet and Megakaryocyte Function

Deletion of GLUT1 and GLUT3 Reveals Multiple Roles for Glucose Metabolism in Platelet and Megakaryocyte Function

Aggressive triple negative breast cancers have unique molecular signature on the basis of mitochondrial genetic and functional defects

Berardinelli-Seip Congenital Lipodystrophy 2/Seipin Is Not Required for Brown Adipogenesis but Regulates Brown Adipose Tissue Development and Function

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