MiT/TFE Family of Transcription Factors: An Evolutionary Perspective

Spina, Martina La; Contreras, Pablo S.; Rissone, Alberto; Meena, Naresh Kumar; Jeong, Eutteum; Martina, José A.

doi:10.3389/fcell.2020.609683

Cited by 60 publications

(39 citation statements)

References 160 publications

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“…The TFEB belongs to the microphthalmia/transcription factor E (MiT/TFE) family of helix–loop–helix-leucine-zipper (bHLH- Zip) proteins. TFEB regulates the expression of genes involved in the autophagy–lysosomal pathway ( Puertollano et al, 2018 ; La Spina et al, 2021 ). It also regulates autophagic flux by promoting and regulating lysosomal and autophagosome biogenesis and regulating autophagosome-lysosome fusion, thereby; facilitating cellular clearance ( Settembre et al, 2011 ).…”

Section: Vital Transcription Factors In Alzheimer’s Diseasementioning

confidence: 99%

Therapeutic Potential of Vital Transcription Factors in Alzheimer’s and Parkinson’s Disease With Particular Emphasis on Transcription Factor EB Mediated Autophagy

et al. 2021

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Autophagy is an important cellular self-digestion and recycling pathway that helps in maintaining cellular homeostasis. Dysregulation at various steps of the autophagic and endolysosomal pathway has been reported in several neurodegenerative disorders such as Alzheimer’s disease (AD), Parkinson’s disease (PD), and Huntington disease (HD) and is cited as a critically important feature for central nervous system (CNS) proteostasis. Recently, another molecular target, namely transcription factor EB (TFEB) has been explored globally to treat neurodegenerative disorders. This TFEB, is a key regulator of autophagy and lysosomal biogenesis pathway. Multiple research studies suggested therapeutic potential by targeting TFEB to treat human diseases involving autophagy-lysosomal dysfunction, especially neurodegenerative disorders. A common observation involving all neurodegenerative disorders is their poor efficacy in clearing and recycle toxic aggregated proteins and damaged cellular organelles due to impairment in the autophagy pathway. This dysfunction in autophagy characterized by the accumulation of toxic protein aggregates leads to a progressive loss in structural integrity/functionality of neurons and may even result in neuronal death. In recent years TFEB, a key regulator of autophagy and lysosomal biogenesis, has received considerable attention. It has emerged as a potential therapeutic target in numerous neurodegenerative disorders like AD and PD. In various neurobiology studies involving animal models, TFEB has been found to ameliorate neurotoxicity and rescue neurodegeneration. Since TFEB is a master transcriptional regulator of autophagy and lysosomal biogenesis pathway and plays a crucial role in defining autophagy activation. Studies have been done to understand the mechanisms for TFEB dysfunction, which may yield insights into how TFEB might be targeted and used for the therapeutic strategy to develop a treatment process with extensive application to neurodegenerative disorders. In this review, we explore the role of different transcription factor-based targeted therapy by some natural compounds for AD and PD with special emphasis on TFEB.

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Section: Vital Transcription Factors In Alzheimer’s Diseasementioning

confidence: 99%

Therapeutic Potential of Vital Transcription Factors in Alzheimer’s and Parkinson’s Disease With Particular Emphasis on Transcription Factor EB Mediated Autophagy

et al. 2021

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“…2 ). TFEB is a member of the microphthalmia‐associated family of the basic helix‐loop‐helix (b‐HLH) leucine zipper transcription factor (MiT/TFE) family of transcription factors, including MiTF, TFE3, TFEB, and TFEC [ 33 ]. Upon activation, TFEB translocates to the nucleus and binds to the coordinated lysosomal expression and regulation (CLEAR, also known as E‐boxes) elements (GTCACGTAC) enriched in the promoter region of numerous lysosomal and autophagic genes, activating the coordinated transcription of these two sets of genes [ 31 , 32 , 34 ].…”

Section: Coordinated Regulation Of Lysosomal Biogenesis and Autophagy...mentioning

confidence: 99%

Lysosomes: multifunctional compartments ruled by a complex regulatory network

2022

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More than 50 years have passed since Nobel laureate Cristian de Duve described for the first time the presence of tiny subcellular compartments filled with hydrolytic enzymes: the lysosome. For a long time, lysosomes were deemed simple waste bags exerting a plethora of hydrolytic activities involved in the recycling of biopolymers, and lysosomal genes were considered to just be simple housekeeping genes, transcribed in a constitutive fashion. However, lysosomes are emerging as multifunctional signalling hubs involved in multiple aspects of cell biology, both under homeostatic and pathological conditions. Lysosomes are involved in the regulation of cell metabolism through the mTOR/TFEB axis. They are also key players in the regulation and onset of the immune response. Furthermore, it is becoming clear that lysosomal hydrolases can regulate several biological processes outside of the lysosome. They are also implicated in a complex communication network among subcellular compartments that involves intimate organelle‐to‐organelle contacts. Furthermore, lysosomal dysfunction is nowadays accepted as the causative event behind several human pathologies: low frequency inherited diseases, cancer, or neurodegenerative, metabolic, inflammatory, and autoimmune diseases. Recent advances in our knowledge of the complex biology of lysosomes have established them as promising therapeutic targets for the treatment of different pathologies. Although recent discoveries have started to highlight that lysosomes are controlled by a complex web of regulatory networks, which in some cases seem to be cell‐ and stimuli‐dependent, to harness the full potential of lysosomes as therapeutic targets, we need a deeper understanding of the little‐known signalling pathways regulating this subcellular compartment and its functions.

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“…The authors also showed that nuclear TFEB favored lysosomal-exocytosis-mediated IL-β secretion, a pro-inflammatory cytokine that has been related to impair insulin secretion and shown to contribute to chronic inflammation reported in type 2 diabetes mellitus patients [ 78 , 79 ], strengthening the idea that although there is evidence that TFEB activation can promote a response that helps the cell to deal with stress, under specific circumstances it could trigger detrimental effects. The C. elegans TFEB ortholog is HLH-30 [ 80 , 81 ]. HLH-30/TFEB is predominantly localized in the cytoplasm under basal conditions and translocates into the nucleus upon several cellular stresses, such as lysosomal impairment, bacterial infection, prolonged endoplasmic reticulum (ER) stress, reactive oxygen species (ROS), and nutrient scarcity [ 82 , 83 , 84 , 85 ].…”

Section: Impacts Of Carbohydrate Metabolism On Lifespanmentioning

confidence: 99%

Effects of High Dietary Carbohydrate and Lipid Intake on the Lifespan of C. elegans

Franco-Juárez

Gómez-Manzo

Hernández-Ochoa

et al. 2021

Cells

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Health and lifespan are influenced by dietary nutrients, whose balance is dependent on the supply or demand of each organism. Many studies have shown that an increased carbohydrate–lipid intake plays a critical role in metabolic dysregulation, which impacts longevity. Caenorhabditis elegans has been successfully used as an in vivo model to study the effects of several factors, such as genetic, environmental, diet, and lifestyle factors, on the molecular mechanisms that have been linked to healthspan, lifespan, and the aging process. There is evidence showing the causative effects of high glucose on lifespan in different diabetic models; however, the precise biological mechanisms affected by dietary nutrients, specifically carbohydrates and lipids, as well as their links with lifespan and longevity, remain unknown. Here, we provide an overview of the deleterious effects caused by high-carbohydrate and high-lipid diets, as well as the molecular signals that affect the lifespan of C. elegans; thus, understanding the detailed molecular mechanisms of high-glucose- and lipid-induced changes in whole organisms would allow the targeting of key regulatory factors to ameliorate metabolic disorders and age-related diseases.

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MiT/TFE Family of Transcription Factors: An Evolutionary Perspective

Cited by 60 publications

References 160 publications

Therapeutic Potential of Vital Transcription Factors in Alzheimer’s and Parkinson’s Disease With Particular Emphasis on Transcription Factor EB Mediated Autophagy

Therapeutic Potential of Vital Transcription Factors in Alzheimer’s and Parkinson’s Disease With Particular Emphasis on Transcription Factor EB Mediated Autophagy

Lysosomes: multifunctional compartments ruled by a complex regulatory network

Effects of High Dietary Carbohydrate and Lipid Intake on the Lifespan of C. elegans

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