From nutritional wealth to autophagy: In vivo metabolic dynamics in the cytosol, mitochondrion and shuttles of IgG producing CHO cells

Junghans, Lisa; Teleki, Attila; Wijaya, Andy; Becker, Max; Schweikert, Michael

doi:10.1016/j.ymben.2019.02.005

Cited by 19 publications

(59 citation statements)

References 76 publications

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“…In addition, a simple combination of alanine and leucine (Leu) mimics the inhibitory effect on autophagy in near-physiological concentrations [31]. Combinations of low concentrations of leucine and proline, Gln, or asparagine also effectively play as inhibitors of cell autophagy [32]. Actually, amino acid metabolism is one of the critical factors in the autophagy process in multiple pathways.…”

Section: Discussionmentioning

confidence: 99%

Estrogen inhibits autophagy and promotes growth of endometrial cancer by promoting glutamine metabolism

et al. 2019

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Background Excessive estrogen exposure is an important pathogenic factor in uterine endometrial cancer (UEC). Recent studies have reported the metabolic properties can influence the progression of UEC. However, the underlying mechanisms have not been fully elucidated. Methods Glutaminase (GLS), MYC and autophagy levels were detected. The biological functions of estrogen-MYC-GLS in UEC cells (UECC) were investigated both in vivo and in vitro. Results Our study showed that estrogen remarkably increased GLS level through up-regulating c-Myc, and enhanced glutamine (Gln) metabolism in estrogen-sensitive UEC cell (UECC), whereas fulvestrant (an ER inhibitor antagonist) could reverse these effects. Estrogen remarkably promoted cell viability and inhibited autophagy of estrogen sensitive UECC. However, CB-839, a potent selective oral bioavailable inhibitor of both splice variants of GLS, negatively regulated Gln metabolism, and inhibited the effects of Gln and estrogen on UECC’s growth and autophagy in vitro and / or in vivo. Conclusions CB-839 triggers autophagy and restricts growth of UEC by suppressing ER/Gln metabolism, which provides new insights into the potential value of CB-839 in clinical treatment of estrogen-related UEC.

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Section: Discussionmentioning

confidence: 99%

Estrogen inhibits autophagy and promotes growth of endometrial cancer by promoting glutamine metabolism

et al. 2019

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“…As a result of this, novel switches to enhance CSPs may be derived. Promising studies focused on metabolism (Handlogten et al, 2018; Junghans et al, 2019; Templeton, Xu, Roush, & Chen, 2017), transcription (Pfizenmaier, Junghans, Teleki, & Takors, 2016; Sha, Bhatia, & Yoon, 2018), and on epigenetics. Epigenetic adaption mechanisms that is histone modification via acetylation and DNA methylation are basic features of CHO cell adaption.…”

Section: Introductionmentioning

confidence: 99%

S‐adenosylmethionine and methylthioadenosine boost cellular productivities of antibody forming Chinese hamster ovary cells

Verhagen

Teleki

Heinrich³

et al. 2020

Biotech & Bioengineering

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The improvement of cell specific productivities for the formation of therapeutic proteins is an important step towards intensified production processes. Among others, the induction of the desired production phenotype via proper media additives is a feasible solution provided that said compounds adequately trigger metabolic and regulatory programs inside the cells. In this study, S-(5′-adenosyl)-L-methionine (SAM) and 5′-deoxy-5′-(methylthio)adenosine (MTA) were found to stimulate cell specific productivities up to approx. 50% while keeping viable cell densities transiently high and partially arresting the cell cycle in an anti-IL-8-producing CHO-DP12 cell line. Noteworthy, MTA turned out to be the chemical degradation product of the methyl group donor SAM and is consumed by the cells.

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“…In addition, a quantification method based on bicratic reverse phase chromatography (RPLC) with acidic mobile phase conditions was applied. For this purpose, an adapted derivatization strategy as well as the respective LC-MS/MS protocol was developed and described by Junghans et al (2019). Therefore, for determination of the intracellular pools of pyruvate, KIV, aKG, and OAA 2.5 µL of a freshly prepared 50 mM phenylhydrazine stock solution were added to 24 µL of the metabolite extracts.…”

Section: Lc-ms Based Analysis Of Intracellular Metabolites' Concentramentioning

confidence: 99%

Identifying and Engineering Bottlenecks of Autotrophic Isobutanol Formation in Recombinant C. ljungdahlii by Systemic Analysis

Hermann

Teleki

Weitz

et al. 2021

Front. Bioeng. Biotechnol.

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Clostridium ljungdahlii (C. ljungdahlii, CLJU) is natively endowed producing acetic acid, 2,3-butandiol, and ethanol consuming gas mixtures of CO2, CO, and H2 (syngas). Here, we present the syngas-based isobutanol formation using C. ljungdahlii harboring the recombinant amplification of the “Ehrlich” pathway that converts intracellular KIV to isobutanol. Autotrophic isobutanol production was studied analyzing two different strains in 3-L gassed and stirred bioreactors. Physiological characterization was thoroughly applied together with metabolic profiling and flux balance analysis. Thereof, KIV and pyruvate supply were identified as key “bottlenecking” precursors limiting preliminary isobutanol formation in CLJU[KAIA] to 0.02 g L–1. Additional blocking of valine synthesis in CLJU[KAIA]:ilvE increased isobutanol production by factor 6.5 finally reaching 0.13 g L–1. Future metabolic engineering should focus on debottlenecking NADPH availability, whereas NADH supply is already equilibrated in the current generation of strains.

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From nutritional wealth to autophagy: In vivo metabolic dynamics in the cytosol, mitochondrion and shuttles of IgG producing CHO cells

Cited by 19 publications

References 76 publications

Estrogen inhibits autophagy and promotes growth of endometrial cancer by promoting glutamine metabolism

Estrogen inhibits autophagy and promotes growth of endometrial cancer by promoting glutamine metabolism

S‐adenosylmethionine and methylthioadenosine boost cellular productivities of antibody forming Chinese hamster ovary cells

Identifying and Engineering Bottlenecks of Autotrophic Isobutanol Formation in Recombinant C. ljungdahlii by Systemic Analysis

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