Autophagy-Dependent Shuttling of TBC1D5 Controls Plasma Membrane Translocation of GLUT1 and Glucose Uptake

Roy, Srirupa; Leidal, Andrew M.; Ye, Jordan; Ronen, Sabrina M.; Debnath, Jayanta

doi:10.1016/j.molcel.2017.05.020

Cited by 131 publications

(146 citation statements)

References 33 publications

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“…Studies by Dikic et al showed that TBC1d5 switches between endosomes and autophagosomes. More recently, the Debnath group extended this study and showed that this switch could modulate retromer function under different physiological conditions such that metabolic stress leads to the association TBC1d5 with autophagosomes, promoting the recycling of GLUT1 and glucose uptake.…”

Section: Tbc1d5 Regulation Of Receptor Traffickingmentioning

confidence: 99%

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Endosomal receptor trafficking: Retromer and beyond

Wang

Fedoseienko

Chen

et al. 2018

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The tubular endolysosomal network is a quality control system that ensures the proper delivery of internalized receptors to specific subcellular destinations in order to maintain cellular homeostasis. Although retromer was originally described in yeast as a regulator of endosome-to-Golgi receptor recycling, mammalian retromer has emerged as a central player in endosome-to-plasma membrane recycling of a variety of receptors. Over the past decade, information regarding the mechanism by which retromer facilitates receptor trafficking has emerged, as has the identification of numerous retromer-associated molecules including the WASH complex, sorting nexins (SNXs) and TBC1d5. Moreover, the recent demonstration that several SNXs can directly interact with retromer cargo to facilitate endosome-to-Golgi retrieval has provided new insight into how these receptors are trafficked in cells. The mechanism by which SNX17 cargoes are recycled out of the endosomal system was demonstrated to involve a retromer-like complex termed the retriever, which is recruited to WASH positive endosomes through an interaction with the COMMD/CCDC22/CCDC93 (CCC) complex. Lastly, the mechanisms by which bacterial and viral pathogens highjack this complex sorting machinery in order to escape the endolysosomal system or remain hidden within the cells are beginning to emerge. In this review, we will highlight recent studies that have begun to unravel the intricacies by which the retromer and associated molecules contribute to receptor trafficking and how deregulation at this sorting domain can contribute to disease or facilitate pathogen infection.

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Section: Tbc1d5 Regulation Of Receptor Traffickingmentioning

confidence: 99%

“…TBC1d5 also plays a role in autophagy, a process in which cellular components are selectively targeted and degraded [27][28][29][30] . Studies by Dikic et al showed that TBC1d5 switches between endosomes and autophagosomes 28,29 .…”

Section: Tbc1d5 Regulation Of Receptor Traffickingmentioning

confidence: 99%

Endosomal receptor trafficking: Retromer and beyond

Wang

Fedoseienko

Chen

et al. 2018

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156

130

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“…Localization of GLUT1 to the cell surface is largely regulated through its endocytic traffic (5)(6)(7)(8)(9)(10)(11), controlled, in non-transformed cells, by cytokine stimulation (12,13) or energy stress (6). In cancer cells, several oncogenic lesions, including hyper activation of the EGFR/PI3K/AKT signaling pathway, induce accumulation of GLUT1 at the cell surface resulting in increased aerobic glycolysis (14)(15)(16).…”

Section: Introductionmentioning

confidence: 99%

High USP6NL Levels in Breast Cancer Sustain Chronic AKT Phosphorylation and GLUT1 Stability Fueling Aerobic Glycolysis

et al. 2018

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USP6NL, also named RN-tre, is a GTPase-activating protein involved in control of endocytosis and signal transduction. Here we report that USP6NL is overexpressed in breast cancer, mainly of the basal-like/integrative cluster 10 subtype. Increased USP6NL levels were accompanied by gene amplification and were associated with worse prognosis in the METABRIC dataset, retaining prognostic value in multivariable analysis. High levels of USP6NL in breast cancer cells delayed endocytosis and degradation of the EGFR, causing chronic AKT (protein kinase B) activation. In turn, AKT stabilized the glucose transporter GLUT1 at the plasma membrane, increasing aerobic glycolysis. In agreement, elevated USP6NL sensitized breast cancer cells to glucose deprivation, indicating that their glycolytic capacity relies on this protein. Depletion of USP6NL accelerated EGFR/AKT downregulation and GLUT1 degradation, impairing cell proliferation exclusively in breast cancer cells that harbored increased levels of USP6NL. Overall, these findings argue that USP6NL overexpression generates a metabolic rewiring that is essential to foster the glycolytic demand of breast cancer cells and promote their proliferation. Significance: USP6NL overexpression leads to glycolysis addiction of breast cancer cells and presents a point of metabolic vulnerability for therapeutic targeting in a subset of aggressive basal-like breast tumors. Graphical Abstract: http://cancerres.aacrjournals.org/content/canres/78/13/3432/F1.large.jpg. Cancer Res; 78(13); 3432–44. ©2018 AACR.

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“…Torin1 (which inhibits both mTORC1 and mTORC2 complexes) was more effective than Rapalink (which is selective for mTORC1) (Rodrik-Outmezguine et al, 2016) in shifting cells toward ETC-dep; the higher sensitivity to Torin-1 is consistent with the role of mTORC2 in enhancing Akt activity. Similarly, the effect of inhibiting autophagy can potentially be explained by the finding that autophagy facilitates glucose transport (Roy et al, 2017). Inhibitors of other metabolic pathways showed lower sensitivity, including those targeting the pentose phosphate pathway (6AN), creatinine phosphate (BU99006), or fatty acid oxidation (etomoxir, PF05175157) ( Figures 4F and S4B).…”

Section: The Balance Between Glycolysis and Protein Translation Regulmentioning

confidence: 99%

Cell-to-cell variability in AMPK activation reveals autonomous cycles in cellular energy balance

Kosaisawe¹,

Sparta²,

Pargett³

et al. 2019

Preprint

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Cellular metabolism can be reconfigured to balance nutrient processing (catabolism) and cellular demands (anabolism). However, the kinetics of reconfiguration within individual mammalian cells, and heterogeneity between cells, have remained unexplored. Using live-cell imaging, we investigate the kinetics of bioenergetic adaptation in individual cells. In response to acute inhibition of oxidative phosphorylation, AMPK substrates are phosphorylated bimodally, identifying cells in different underlying states of anabolism and catabolism.Manipulation of glycolysis, insulin/Akt signaling, or protein synthesis shifts the distribution of these states.Long-term lineage analysis confirms that this cellular energy balance cycles over time within individual cells, independently of the cell division cycle. We further demonstrate that AMPK inhibits the ERK and mTOR cell growth signaling pathways specifically when anabolism is in excess. Our results reveal dynamic fluctuations of energetic balance, establish distinct time scales of cellular energetic control, and open opportunities for more precise prediction and control of cellular metabolic functions.

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Autophagy-Dependent Shuttling of TBC1D5 Controls Plasma Membrane Translocation of GLUT1 and Glucose Uptake

Cited by 131 publications

References 33 publications

Endosomal receptor trafficking: Retromer and beyond

Endosomal receptor trafficking: Retromer and beyond

High USP6NL Levels in Breast Cancer Sustain Chronic AKT Phosphorylation and GLUT1 Stability Fueling Aerobic Glycolysis

Cell-to-cell variability in AMPK activation reveals autonomous cycles in cellular energy balance

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