Glycolysis: a bioenergetic or a survival pathway?

Bolaños, Juan P.; Almeida, Ángeles; Moncada, Salvador

doi:10.1016/j.tibs.2009.10.006

Cited by 313 publications

(244 citation statements)

References 50 publications

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“…Sections were fixed in 4% paraformaldehyde in PBS for 20 min at room temperature, washed with PBS, and treated with 0.1 M chain complex activity in antioxidant-treated Drp1KO Purkinje cells. However, because neurons are highly dependent on oxidative phosphorylation (Bolaños et al, 2010), it is reasonable to assume that this process is at least partially maintained at a level that is sufficient to support survival of Purkinje cells. In addition to oxidative damage, enlargement may affect mitochondrial functions by changing the volume-to-surface ratio of this organelle.…”

Section: Immunofluorescence Of Cerebellar Sectionsmentioning

confidence: 99%

Mitochondrial division ensures the survival of postmitotic neurons by suppressing oxidative damage

Kageyama¹,

Zhang²,

Roda³

et al. 2012

J Exp Med

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Section: Immunofluorescence Of Cerebellar Sectionsmentioning

confidence: 99%

Mitochondrial division ensures the survival of postmitotic neurons by suppressing oxidative damage

Kageyama¹,

Zhang²,

Roda³

et al. 2012

J Exp Med

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“…Inactivation of APC/C-Cdh1 in G1 of the cell cycle is necessary for initiation of S phase, in which DNA is replicated and chromosomes are duplicated. We have recently found that APC/CCdh1 links cell cycle activity with that of the enzyme 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase isoform 3 (PFKFB3) (9,10). PFKFB3-a key regulator of glycolysis (11)-contains a KEN box motif and is thus also broken down by APC/C-Cdh1.…”

mentioning

confidence: 99%

Anaphase-promoting complex/cyclosome-Cdh1 coordinates glycolysis and glutaminolysis with transition to S phase in human T lymphocytes

Colombo

Palacios-Callender

Frakich

et al. 2010

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

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108

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Cell proliferation is accompanied by an increase in the utilization of glucose and glutamine. The proliferative response is dependent on a decrease in the activity of the ubiquitin ligase anaphasepromoting complex/cyclosome (APC/C)-Cdh1 which controls G1-to-S-phase transition by targeting degradation motifs, notably the KEN box. This occurs not only in cell cycle proteins but also in the glycolysis-promoting enzyme 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase isoform 3 (PFKFB3), as we have recently demonstrated in cells in culture. We now show that APC/C-Cdh1 controls the proliferative response of human T lymphocytes. Moreover, we have found that glutaminase 1 is a substrate for this ubiquitin ligase and appears at the same time as PFKFB3 in proliferating T lymphocytes. Glutaminase 1 is the first enzyme in glutaminolysis, which converts glutamine to lactate, yielding intermediates for cell proliferation. Thus APC/C-Cdh1 is responsible for the provision not only of glucose but also of glutamine and, as such, accounts for the critical step that links the cell cycle with the metabolic substrates essential for its progression.cell cycle | glutaminase | 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase isoform 3 | proliferation H uman blood T lymphocytes have been used for many years in studies of cell proliferation (1, 2). These cells can be obtained directly from the circulation and therefore avoid the pitfalls associated with the use of cells in culture, which acquire confounding characteristics as a result of their in vitro environment (3). Interest has recently been rekindled in the metabolic changes that underpin cell proliferation in cancer to identify potential targets for chemotherapy (4,5). This has highlighted the need to carry out comparative studies on proliferating normal and tumor cells to ascertain whether an antimetabolic approach to cancer is possible without side effects related to the mechanism of action.The E3 ubiquitin ligase anaphase-promoting complex/cyclosome (APC/C) attached to the activator protein Cdh1 plays a crucial role in controlling G1-to S-phase transition, and therefore proliferation, through the breakdown of cell cycle proteins (6, 7). APC/C-Cdh1 substrates are targeted for degradation through specific recognition motifs, including one known as the KEN box (8). Inactivation of APC/C-Cdh1 in G1 of the cell cycle is necessary for initiation of S phase, in which DNA is replicated and chromosomes are duplicated. We have recently found that APC/CCdh1 links cell cycle activity with that of the enzyme 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase isoform 3 (PFKFB3) (9, 10). PFKFB3-a key regulator of glycolysis (11)-contains a KEN box motif and is thus also broken down by APC/C-Cdh1. Inactivation of APC/C-Cdh1 enables PFKFB3 to up-regulate glycolysis, thus providing the cell with the glucose essential for the subsequent biosynthesis of macromolecules. Our previous studies (9) were carried out in two cell lines; we therefore decided to investigate whether the same mechanis...

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“…For instance, through enhanced cell viability by increasing cellular ATP levels through the glycolytic pathway or by increasing NADPH, through the pentose phosphate pathway. 8 Both pathways have been suggested to inhibit caspase activation in other cell types. 9,10 Glucose has also been shown to induce direct binding of hexokinase to the voltage-dependent anion channel (VDAC) in mitochondria blocking cytochrome c release and prevent apoptosis.…”

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confidence: 99%

Anti-apoptotic effect of hyperglycemia can allow survival of potentially autoreactive T cells

2010

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Thymocyte development is a tightly controlled multi-step process involving selective elimination of self-reactive and nonfunctional T cells by apoptosis. This developmental process depends on signaling by Notch, IL-7 and active glucose metabolism. In this study, we explored the requirement of glucose for thymocyte survival and found that in addition to metabolic regulation, glucose leads to the expression of anti-apoptotic genes. Under hyperglycemic conditions, both mouse and human thymocytes demonstrate enhanced survival. We show that glucose-induced anti-apoptotic genes are dependent on NF-jB p65 because high glucose is unable to attenuate normal ongoing apoptosis of thymocytes isolated from p65 knockout mice. Furthermore, we demonstrate that in vivo hyperglycemia decreases apoptosis of thymocytes allowing for survival of potentially self-reactive thymocytes. These results imply that hyperglycemic conditions could contribute to the development of autoimmunity through dysregulated thymic selection.

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Glycolysis: a bioenergetic or a survival pathway?

Cited by 313 publications

References 50 publications

Mitochondrial division ensures the survival of postmitotic neurons by suppressing oxidative damage

Mitochondrial division ensures the survival of postmitotic neurons by suppressing oxidative damage

Anaphase-promoting complex/cyclosome-Cdh1 coordinates glycolysis and glutaminolysis with transition to S phase in human T lymphocytes

Anti-apoptotic effect of hyperglycemia can allow survival of potentially autoreactive T cells

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