Metabolic sensors and their interplay with cell signalling and transcription

Krejčı́, Alena

doi:10.1042/bst20110767

Cited by 19 publications

(11 citation statements)

References 121 publications

(133 reference statements)

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“…By contrast, in Sarno, the niche of origin for the SM ecotype, a low induction of transcription and post-translational events are required. In addition, various metabolic sensing and feedback mechanisms could be able to mediate appropriate responses in crucial cellular processes, such as cell signaling, chromatin structure/function and ultimately gene expression [53]. …”

Section: Discussionmentioning

confidence: 99%

Unraveling the complexity of transcriptomic, metabolomic and quality environmental response of tomato fruit

et al. 2017

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BackgroundThe environment has a profound influence on the organoleptic quality of tomato (Solanum lycopersicum) fruit, the extent of which depends on a well-regulated and dynamic interplay among genes, metabolites and sensorial attributes. We used a systems biology approach to elucidate the complex interacting mechanisms regulating the plasticity of sensorial traits. To investigate environmentally challenged transcriptomic and metabolomic remodeling and evaluate the organoleptic consequences of such variations we grown three tomato varieties, Heinz 1706, whose genome was sequenced as reference and two “local” ones, San Marzano and Vesuviano in two different locations of Campania region (Italy).ResultsResponses to environment were more pronounced in the two “local” genotypes, rather than in the Heinz 1706. The overall genetic composition of each genotype, acting in trans, modulated the specific response to environment. Duplicated genes and transcription factors, establishing different number of network connections by gaining or losing links, play a dominant role in shaping organoleptic profile. The fundamental role of cell wall metabolism in tuning all the quality attributes, including the sensorial perception, was also highlighted.ConclusionsAlthough similar fruit-related quality processes are activated in the same environment, different tomato genotypes follow distinct transcriptomic, metabolomic and sensorial trajectories depending on their own genetic makeup.Electronic supplementary materialThe online version of this article (doi:10.1186/s12870-017-1008-4) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

Unraveling the complexity of transcriptomic, metabolomic and quality environmental response of tomato fruit

et al. 2017

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“…Principally, the Warburg effect reinstates how cancer cells would supplement their metabolic requirements [46, 47]. It has been shown that cancer cells exhibit heterogeneous metabolic rewiring beyond the Warburg effect suggesting that this heterogeneity is a manifestation of different metabolic adaptations by cancer cells.…”

Section: Discussionmentioning

confidence: 99%

“…The seminal studies regarding CLL metabolism suggested that compared to normal lymphocytes, CLL lymphocytes consumed less glucose in a similar manner than lymphocytes from patients with diabetes mellitus [46, 47, 51, 52]. In contrast to these early studies, a recent metabolomic study using freshly isolated CLL lymphocytes revealed that these malignant lymphocytes display high levels of aerobic glycolysis and produce lactate which are consistent with the use of glucose and the Warburg effect [53].…”

Section: Discussionmentioning

confidence: 99%

Resistance to Dasatinib in primary chronic lymphocytic leukemia lymphocytes involves AMPK-mediated energetic re-programming

Marignac

Smith²,

Toban³

et al. 2013

Oncotarget

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Chronic lymphocytic leukemia (CLL) is the most common leukemia in adults in the western world. Although promising new therapies for this incurable disease are being tested in clinical trials, the therapeutic relevance of metabolic rewiring in chronic lymphocytic leukemia (CLL) is poorly understood. The aim of this study was to identify targetable metabolic differences in primary CLL lymphocytes by the use of Dasatinib. Dasatinib is a multi-tyrosine kinase inhibitor used to treat chronic myelogenous leukemia (CML) and is being tested in clinical trials for several cancers including CLL. This drug has been shown to be beneficial to CML patients suffering from diabetes by reducing their glucose plasma levels. In keeping with this previous observation, we report that Dasatinib induced glucose use while reducing lactate production, suggesting that this tyrosine kinase inhibitor decreases aerobic glycolysis and shifts glucose use in primary CLL lymphocytes. Our results suggest that primary CLL lymphocytes (independently of traditional prognostic factors) can be stratified in two subsets by their sensitivity to Dasatinib in vitro. Increased glucose use induced by Dasatinib or by inhibition of mitochondrial respiration was not sufficient to sustain survival and ATP levels in CLL samples sensitive to Dasatinib. The two subsets of primary CLL lymphocytes are characterized as well by a differential dependency on mitochondrial respiration and the use of anabolic or catabolic processes to cope with induced metabolic/energetic stress. Differential metabolic reprogramming between subsets is supported by the contrasting effect on the survival of Dasatinib treated CLL lymphocytes with pharmacological inhibition of two master metabolic regulators (mTorc1 and AMPK) as well as induced autophagy. Alternative metabolic organization between subsets is further supported by the differential basal expression (freshly purified lymphocytes) of active AMPK, regulators of glucose metabolism and modulators of AKT signaling. The contrasting metabolic features revealed by our strategy could be used to metabolically target CLL lymphocyte subsets creating new therapeutic windows for this disease for mTORC1 or AMPK inhibitors. Indeed, we report that Metformin, a drug used to treat diabetes was selectively cytotoxic to Dasatinib sensitive samples. Ultimately, we suggest that a similar strategy could be applied to other cancer types by using Dasatinib and/or relevant tyrosine kinase inhibitors.

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“…Warburg reasoned that respiration must be damaged in cancers because high levels of O 2 are unable to suppress the production of lactic acid by cancer cells (known as the Pasteur effect). However, new studies have demonstrated that tumor mitochondria are fairly functional with regards to respiration and ATP synthesis, exhibiting almost normal respiratory control ratios and capabilities for the oxidation of respiratory substrates (Bensinger and Christofk 2012; Eakin, et al 1972; Krejci 2012; Nakajima and Van Houten 2012). …”

Section: Introductionmentioning

confidence: 99%

Current views on cell metabolism in SDHx-related pheochromocytoma and paraganglioma

Vícha¹,

Taïeb²,

Pacák³

2014

Endocrine-Related Cancer

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Warburg’s metabolic hypothesis is based on the assumption that a cancer cell’s respiration must be under attack, leading to its damage, in order to obtain increased glycolysis. Although this may not apply to all cancers, there is some evidence proving that primarily abnormally functioning mitochondrial complexes are indeed related to cancer development. Thus, mutations in complex II (succinate dehydrogenase (SDH)) lead to the formation of pheochromocytoma/paraganglioma. Mutations in one of the SDH genes (SDHx mutations) lead to succinate accumulation associated with very low fumarate levels, increased glutaminolysis, the generation of reactive oxygen species (ROS), and pseudohypoxia. This results in significant changes in signaling pathways (many of them dependent on the stabilization of hypoxia-inducible factor (HIF)) including oxidative phosphorylation, glycolysis, specific expression profiles, as well as genomic instability and increased mutability resulting in tumor development. Although there is currently no very effective therapy for SDHx-related metastatic pheochromocytomas/paragangliomas, targeting their fundamental metabolic abnormalities may provide a unique opportunity for the development of novel and more effective forms of therapy for these tumors.

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Metabolic sensors and their interplay with cell signalling and transcription

Cited by 19 publications

References 121 publications

Unraveling the complexity of transcriptomic, metabolomic and quality environmental response of tomato fruit

Unraveling the complexity of transcriptomic, metabolomic and quality environmental response of tomato fruit

Resistance to Dasatinib in primary chronic lymphocytic leukemia lymphocytes involves AMPK-mediated energetic re-programming

Current views on cell metabolism in SDHx-related pheochromocytoma and paraganglioma

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