Transcription factor EB regulates cardiovascular homeostasis

Lu, Haocheng; Sun, Jin; Hamblin, Milton; Chen, Y. Eugene; Fan, Yanbo

doi:10.1016/j.ebiom.2020.103207

Cited by 23 publications

(15 citation statements)

References 73 publications

(67 reference statements)

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“…TFEB, which controls the lysosomal–autophagic pathway, has been shown to be efficient in delaying the advancement of lysosome-related disorders such as cancer [ 193 ]. Furthermore, a recent study highlighted several chemicals discovered in recent years that influence the expression or nuclear translocation of TFEB, including 3,4-dimethoxychalcone (3,4-DC), 2-hydoxypropyl-cyclodextrin (HPCD), and digoxin [ 194 , 195 ].…”

Section: Targeting Lysosomes In Amlmentioning

confidence: 99%

Lysosomes in Stem Cell Quiescence: A Potential Therapeutic Target in Acute Myeloid Leukemia

Jain

Bose

Arya

et al. 2022

Cancers

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Lysosomes are cellular organelles that regulate essential biological processes such as cellular homeostasis, development, and aging. They are primarily connected to the degradation/recycling of cellular macromolecules and participate in cellular trafficking, nutritional signaling, energy metabolism, and immune regulation. Therefore, lysosomes connect cellular metabolism and signaling pathways. Lysosome’s involvement in the critical biological processes has rekindled clinical interest towards this organelle for treating various diseases, including cancer. Recent research advancements have demonstrated that lysosomes also regulate the maintenance and hemostasis of hematopoietic stem cells (HSCs), which play a critical role in the progression of acute myeloid leukemia (AML) and other types of cancer. Lysosomes regulate both HSCs’ metabolic networks and identity transition. AML is a lethal type of blood cancer with a poor prognosis that is particularly associated with aging. Although the genetic landscape of AML has been extensively described, only a few targeted therapies have been produced, warranting the need for further research. This review summarizes the functions and importance of targeting lysosomes in AML, while highlighting the significance of lysosomes in HSCs maintenance.

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Section: Targeting Lysosomes In Amlmentioning

confidence: 99%

Lysosomes in Stem Cell Quiescence: A Potential Therapeutic Target in Acute Myeloid Leukemia

Jain

Bose

Arya

et al. 2022

Cancers

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“…The role of MiT transcription factors in modulating cellular homeostasis has made them a target of interest for many pathological conditions with a metabolic background, such as lysosomal storage disorders [ 148 , 201 ], cardiovascular disease [ 202 ], and NDD. Not long after the description of TFEB as central protein in a gene network regulating lysosomal biogenesis and function, it was shown that enhancing lysosomal biogenesis in cellular and animal models of PD can increase autophagolysosomal clearance and attenuate cell death.…”

Section: Main Textmentioning

confidence: 99%

Crosstalk of organelles in Parkinson’s disease – MiT family transcription factors as central players in signaling pathways connecting mitochondria and lysosomes

Lang

Pramstaller

Pichler

2022

Mol Neurodegeneration

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Living organisms constantly need to adapt to their surrounding environment and have evolved sophisticated mechanisms to deal with stress. Mitochondria and lysosomes are central organelles in the response to energy and nutrient availability within a cell and act through interconnected mechanisms. However, when such processes become overwhelmed, it can lead to pathologies. Parkinson’s disease (PD) is a common neurodegenerative disorder (NDD) characterized by proteinaceous intracellular inclusions and progressive loss of dopaminergic neurons, which causes motor and non-motor symptoms. Genetic and environmental factors may contribute to the disease etiology. Mitochondrial dysfunction has long been recognized as a hallmark of PD pathogenesis, and several aspects of mitochondrial biology are impaired in PD patients and models. In addition, defects of the autophagy-lysosomal pathway have extensively been observed in cell and animal models as well as PD patients’ brains, where constitutive autophagy is indispensable for adaptation to stress and energy deficiency. Genetic and molecular studies have shown that the functions of mitochondria and lysosomal compartments are tightly linked and influence each other. Connections between these organelles are constituted among others by mitophagy, organellar dynamics and cellular signaling cascades, such as calcium (Ca2+) and mTOR (mammalian target of rapamycin) signaling and the activation of transcription factors. Members of the Microphthalmia-associated transcription factor family (MiT), including MITF, TFE3 and TFEB, play a central role in regulating cellular homeostasis in response to metabolic pressure and are considered master regulators of lysosomal biogenesis. As such, they are part of the interconnection between mitochondria and lysosome functions and therefore represent attractive targets for therapeutic approaches against NDD, including PD. The activation of MiT transcription factors through genetic and pharmacological approaches have shown encouraging results at ameliorating PD-related phenotypes in in vitro and in vivo models. In this review, we summarize the relationship between mitochondrial and autophagy-lysosomal functions in the context of PD etiology and focus on the role of the MiT pathway and its potential as pharmacological target against PD.

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“…In total, more than 400 TFEB target genes have been identified, many of which are directly associated with the activation of lysosomes and autophagy. These include lysosomal hydrolase and accessory protein genes, lysosomal membrane protein base domains, lysosomal V-ATPase pump genes, and lysosomal biosynthesis regulator genes [ 110 ]. Lysosomes are organelles with digestive and transport functions that regulate calcium channels, and calcium ion imbalance may disrupt lysosome function.…”

Section: Mitophagymentioning

confidence: 99%

“…Factor EB in Mitochondrial Autophagy. Transcription factor EB (TFEB), a member of the MiTF/TFE family of leucine zipper transcription factors, plays an important role in the regulation of autophagy [110]. Transcription of TFEB can activate the autophagy pathway; induce the expression of key genes in the stages of autophagic vesicle formation, autophagic vesicle extension, content recognition, and content degradation; and control the activation of autophagy/ mitophagy [111].…”

Section: Regulatory Mechanism and Function Of Transcriptionmentioning

confidence: 99%

Protective Effect of Natural Medicinal Plants on Cardiomyocyte Injury in Heart Failure: Targeting the Dysregulation of Mitochondrial Homeostasis and Mitophagy

Wang

Liu

2022

Oxidative Medicine and Cellular Longevity

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Heart failure occurs because of various cardiovascular pathologies, such as coronary artery disease or cardiorenal syndrome, eventually reaching end-stage disease. Various factors contribute to cardiac structural or functional changes that result in systolic or diastolic dysfunction. Several studies have confirmed that the key factor in heart failure progression is myocardial cell death, and mitophagy is the major mechanism regulating myocardial cell death in heart failure. The clinical mechanisms of heart failure are well understood in practice. However, the essential role of mitophagic regulation in heart failure has only recently received widespread attention. Receptor-mediated mitophagy is involved in various mitochondrial processes like oxidative stress injury, energy metabolism disorders, and calcium homeostasis, which are also the main causes of heart failure. Understanding of the diverse regulatory mechanisms in mitophagy and the complexity of its pathophysiology in heart failure remains incomplete. Related studies have found that various natural medicinal plants and active ingredients, such as flavonoids and saponins, can regulate mitophagy to a certain extent, improve myocardial function, and protect myocardial cells. This review comprehensively covers the relevant mechanisms of different types of mitophagy in regulating heart failure pathology and controlling mitochondrial adaptability to stress injury. Further, it explores the relationship between mitophagy and cardiac ejection dysfunction. Natural medicinal plant-targeted regulation strategies and scientific evidence on mitophagy were provided to elucidate current and potential strategies to apply mitophagy-targeted therapy for heart failure.

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Transcription factor EB regulates cardiovascular homeostasis

Cited by 23 publications

References 73 publications

Lysosomes in Stem Cell Quiescence: A Potential Therapeutic Target in Acute Myeloid Leukemia

Lysosomes in Stem Cell Quiescence: A Potential Therapeutic Target in Acute Myeloid Leukemia

Crosstalk of organelles in Parkinson’s disease – MiT family transcription factors as central players in signaling pathways connecting mitochondria and lysosomes

Protective Effect of Natural Medicinal Plants on Cardiomyocyte Injury in Heart Failure: Targeting the Dysregulation of Mitochondrial Homeostasis and Mitophagy

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