Erratum: TFEB controls cellular lipid metabolism through a starvation-induced autoregulatory loop

Settembre, Carmine; Cegli, Rossella De; Mansueto, Gelsomina; Saha, Pradip Kumar; Vetrini, Francesco; Visvikis, Orane; Huynh, Tuong; Carissimo, Annamaria; Palmer, D. Jason; Klisch, Tiemo J.; Wollenberg, Amanda C.; Bernardo, Diego di; Irazoqui, Javier E.; Ballabio, Andrea

doi:10.1038/ncb2814

Cited by 15 publications

(6 citation statements)

References 34 publications

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“…Unlike in yeast and mammals, where TOR has been shown to directly phosphorylate several ATG proteins to regulate autophagy (ATG13, Ulk1/ATG1, and AGT14) (Jung et al 2009(Jung et al , 2010Russell et al 2013Russell et al , 2014, phosphorylation of corresponding proteins in C. elegans by TOR has not been biochemically demonstrated. In addition, consistent with studies in mammalian cells, regulation of the mRNA levels of lgg-1 and other autophagy genes by TORC1 is at least partly mediated by the transcription factor HLH-30/TFEB in C. elegans (Lapierre et al 2013;Settembre et al 2013;Nakamura et al 2016). Phosphorylation of TFEB by TORC1 regulates its subcellular localization and activity in mammals, but this has not yet been demonstrated in C. elegans (Napolitano and Ballabio 2016).…”

Section: Downstream Targetssupporting

confidence: 71%

TOR Signaling in Caenorhabditis elegans Development, Metabolism, and Aging

et al. 2019

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The Target of Rapamycin (TOR or mTOR) is a serine/threonine kinase that regulates growth, development, and behaviors by modulating protein synthesis, autophagy, and multiple other cellular processes in response to changes in nutrients and other cues. Over recent years, TOR has been studied intensively in mammalian cell culture and genetic systems because of its importance in growth, metabolism, cancer, and aging. Through its advantages for unbiased, and high-throughput, genetic and in vivo studies, Caenorhabditis elegans has made major contributions to our understanding of TOR biology. Genetic analyses in the worm have revealed unexpected aspects of TOR functions and regulation, and have the potential to further expand our understanding of how growth and metabolic regulation influence development. In the aging field, C. elegans has played a leading role in revealing the promise of TOR inhibition as a strategy for extending life span, and identifying mechanisms that function upstream and downstream of TOR to influence aging. Here, we review the state of the TOR field in C. elegans, and focus on what we have learned about its functions in development, metabolism, and aging. We discuss knowledge gaps, including the potential pitfalls in translating findings back and forth across organisms, but also describe how TOR is important for C. elegans biology, and how C. elegans work has developed paradigms of great importance for the broader TOR field.

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Section: Downstream Targetssupporting

confidence: 71%

TOR Signaling in Caenorhabditis elegans Development, Metabolism, and Aging

et al. 2019

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“…CD45.1 + (RRID: IMSR_JAX:002014), C57BL/6J (RRID: IMSR_JAX:000664), and Rag1 −/− (RRID: IMSR_JAX:002216), B6.129S2- Ighm tm1Cgn /J (RRID:IMSR_JAX:002288) and B6.129P2- Aicda tm1(cre)Mnz /J (RRID:IMSR_JAX:007770) mice were purchased from the Jackson Laboratory. Tfeb fl/fl mouse was a gift from Dr. Andrea Ballabio (Telethon Institute of Genetics and Medicine)( 71 ). Tfe3 −/− mouse was a gift from Dr. Ming O. Li (Memorial Sloan Kettering Cancer Center)( 31 ).…”

Section: Methodsmentioning

confidence: 99%

“…Tfeb fl/fl mouse was a gift from Dr. Andrea Ballabio (Telethon Institute of Genetics and Medicine)(71). Tfe3 -/mouse was a gift from Dr. Ming O. Li (Memorial Sloan Kettering Cancer Center)(31).…”

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confidence: 99%

The nutrient-sensing Rag-GTPase complex in B cells controls humoral immunity via TFEB/TFE3-dependent mitochondrial fitness

Zhu,

Wu,

et al. 2024

Preprint

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During the humoral immune response, B cells undergo rapid metabolic reprogramming with a high demand for nutrients, which are vital to sustain the formation of the germinal centers (GCs). Rag-GTPases sense amino acid availability to modulate the mechanistic target of rapamycin complex 1 (mTORC1) pathway and suppress transcription factor EB (TFEB) and transcription factor enhancer 3 (TFE3), members of the microphthalmia (MiT/TFE) family of HLH-leucine zipper transcription factors. However, how Rag-GTPases coordinate amino acid sensing, mTORC1 activation, and TFEB/TFE3 activity in humoral immunity remains undefined. Here, we show that B cell-intrinsic Rag-GTPases are critical for the development and activation of B cells. RagA/RagB deficient B cells fail to form GCs, produce antibodies, and generate plasmablasts in both T-dependent (TD) and T-independent (TI) humoral immune responses. Deletion of RagA/RagB in GC B cells leads to abnormal dark zone (DZ) to light zone (LZ) ratio and reduced affinity maturation. Mechanistically, the Rag-GTPase complex constrains TFEB/TFE3 activity to prevent mitophagy dysregulation and maintain mitochondrial fitness in B cells, which are independent of canonical mTORC1 activation. TFEB/TFE3 deletion restores B cell development, GC formation in Peyer's patches and TI humoral immunity, but not TD humoral immunity in the absence of Rag-GTPases. Collectively, our data establish Rag-GTPase-TFEB/TFE3 pathway as an mTORC1 independent mechanism to coordinating nutrient sensing and mitochondrial metabolism in B cells.

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“…Transcription factor EB (TFEB) belongs to the microphthalmia (MiT/TFE) family, which contains the basic helix-loop-helix leucine-zipper motif (bHLH-Zip) [ 5 , 6 ]. TFEB is crucially involved in lysosomal biogenesis [ 7 ], lysosomal exocytosis [ 8 ], autophagy [ 9 ], lipid catabolism [ 10 ], energy metabolism [ 11 ], angiogenesis [ 12 ], and the immune response [ 13 ]. Furthermore, TFEB is protective against myocardial ischemia [ 14 ], inflammatory responses [ 13 ], and atherosclerosis [ 15 ].…”

Section: Introductionmentioning

confidence: 99%

Transcription Factor EB: A Promising Therapeutic Target for Ischemic Stroke

Shao

Lang

Ding

et al. 2024

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Transcription factor EB (TFEB) is an important endogenous defensive protein that responds to ischemic stimuli. Acute ischemic stroke is a growing concern due to its high morbidity and mortality. Most survivors suffer from disabilities such as numbness or weakness in an arm or leg, facial droop, difficulty speaking or understanding speech, confusion, impaired balance or coordination, or loss of vision. Although TFEB plays a neuroprotective role, its potential effect on ischemic stroke remains unclear. This article describes the basic structure, regulation of transcriptional activity, and biological roles of TFEB relevant to ischemic stroke. Additionally, we explore the effects of TFEB on the various pathological processes underlying ischemic stroke and current therapeutic approaches. The information compiled here may inform clinical and basic studies on TFEB, which may be an effective therapeutic drug target for ischemic stroke.

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Erratum: TFEB controls cellular lipid metabolism through a starvation-induced autoregulatory loop

Cited by 15 publications

References 34 publications

TOR Signaling in Caenorhabditis elegans Development, Metabolism, and Aging

TOR Signaling in Caenorhabditis elegans Development, Metabolism, and Aging

The nutrient-sensing Rag-GTPase complex in B cells controls humoral immunity via TFEB/TFE3-dependent mitochondrial fitness

Transcription Factor EB: A Promising Therapeutic Target for Ischemic Stroke

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