TFEB: A Emerging Regulator in Lipid Homeostasis for Atherosclerosis

Li, Manman; Wang, Zi-Tong; Wang, Pengyu; Li, Hong; Yang, Liming

doi:10.3389/fphys.2021.639920

Cited by 9 publications

(6 citation statements)

References 119 publications

(85 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Recent years have witnessed the emergence of MiT transcription factors as key regulators of innate immunity genes during a wide range of disease conditions, including infections by bacteria and viruses and chronic inflammation ( 1 ). Mostly thought of as master regulators of lysosomal biogenesis and autophagy, their functions include positive regulation of lipid mobilization and cytokine induction ( 2 – 9 ). While overall the genes that MiT factors control in different scenarios are becoming better understood, their mechanisms of regulation and action are much less so.…”

Section: Introductionmentioning

confidence: 99%

C. elegans orphan nuclear receptor NHR-42 represses innate immunity and promotes lipid loss downstream of HLH-30/TFEB

Goswamy

Gonzalez²,

Labed³

et al. 2023

Front. Immunol.

View full text Add to dashboard Buy / Rent full text

In recent years, transcription factors of the Microphthalmia-TFE (MiT) family, including TFEB and TFE3 in mammals and HLH-30 in Caenorhabditis elegans, have emerged as important regulators of innate immunity and inflammation in invertebrates and vertebrates. Despite great strides in knowledge, the mechanisms that mediate downstream actions of MiT transcription factors in the context of innate host defense remain poorly understood. Here, we report that HLH-30, which promotes lipid droplet mobilization and host defense, induces the expression of orphan nuclear receptor NHR-42 during infection with Staphylococcus aureus. Remarkably, NHR-42 loss of function promoted host infection resistance, genetically defining NHR-42 as an HLH-30-controlled negative regulator of innate immunity. During infection, NHR-42 was required for lipid droplet loss, suggesting that it is an important effector of HLH-30 in lipid immunometabolism. Moreover, transcriptional profiling of nhr-42 mutants revealed wholesale activation of an antimicrobial signature, of which abf-2, cnc-2, and lec-11 were important for the enhanced survival of infection of nhr-42 mutants. These results advance our knowledge of the mechanisms by which MiT transcription factors promote host defense, and by analogy suggest that TFEB and TFE3 may similarly promote host defense via NHR-42-homologous nuclear receptors in mammals.

show abstract

Section: Introductionmentioning

confidence: 99%

C. elegans orphan nuclear receptor NHR-42 represses innate immunity and promotes lipid loss downstream of HLH-30/TFEB

Goswamy

Gonzalez²,

Labed³

et al. 2023

Front. Immunol.

View full text Add to dashboard Buy / Rent full text

show abstract

“…Nevertheless, stress-related circumstances like lysosomal malfunction or starvation cause TFEB to move to the nuclei of cells, in which it stimulates the expression of the target genes. 8 , 11 – 13 …”

Section: Introductionmentioning

confidence: 99%

“… 69 However, small ubiquitin-like modifier (SUMOylation), a reversible post-translational modification, of TFEB at a lysine residue could result in a reduction in transcriptional activity. 13 , 49 , 70 The expression of TFEB can also be self-regulated. 49 …”

Section: Introductionmentioning

confidence: 99%

Transcription factor EB as a key molecular factor in human health and its implication in diseases

Gebrie

2023

SAGE Open Medicine

View full text Add to dashboard Buy / Rent full text

Transcription factor EB, as a component of the microphthalmia family of transcription factors, has been demonstrated to be a key controller of autophagy–lysosomal biogenesis. Transcription factor EB is activated by stressors such as nutrition and deprivation of growth factors, hypoxia, lysosomal stress, and mitochondrial injury. To achieve the ultimate functional state, it is controlled in a variety of modes, such as in its rate of transcription, post-transcriptional control, and post-translational alterations. Due to its versatile role in numerous signaling pathways, including the Wnt, calcium, AKT, and mammalian target of rapamycin complex 1 signaling pathways, transcription factor EB—originally identified to be an oncogene—is now well acknowledged as a regulator of a wide range of physiological systems, including autophagy–lysosomal biogenesis, response to stress, metabolism, and energy homeostasis. The well-known and recently identified roles of transcription factor EB suggest that this protein might play a central role in signaling networks in a number of non-communicable illnesses, such as cancer, cardiovascular disorders, drug resistance mechanisms, immunological disease, and tissue growth. The important developments in transcription factor EB research since its first description are described in this review. This review helps to advance transcription factor EB from fundamental research into therapeutic and regenerative applications by shedding light on how important a role it plays in human health and disease at the molecular level.

show abstract

“…Multiple other roles have been associated with the members of the MiTF/TFE family, including the regulation of mitophagy [ 7 ], lipid catabolism [ 8 , 9 ], and mitochondrial biogenesis [ 10 ]. Although some of their activities may overlap, each homolog of the MiTF/TFE family seems to have a specific pattern of expression and individual functions, which will be addressed in the following sections.…”

Section: Introductionmentioning

confidence: 99%

The Regulation of MiTF/TFE Transcription Factors Across Model Organisms: from Brain Physiology to Implication for Neurodegeneration

Agostini

Agostinis²,

Medina³

et al. 2022

Mol Neurobiol

View full text Add to dashboard Buy / Rent full text

The microphthalmia/transcription factor E (MiTF/TFE) transcription factors are responsible for the regulation of various key processes for the maintenance of brain function, including autophagy-lysosomal pathway, lipid catabolism, and mitochondrial homeostasis. Among them, autophagy is one of the most relevant pathways in this frame; it is evolutionary conserved and crucial for cellular homeostasis. The dysregulation of MiTF/TFE proteins was shown to be involved in the development and progression of neurodegenerative diseases. Thus, the characterization of their function is key in the understanding of the etiology of these diseases, with the potential to develop novel therapeutics targeted to MiTF/TFE proteins and to the autophagic process. The fact that these proteins are evolutionary conserved suggests that their function and dysfunction can be investigated in model organisms with a simpler nervous system than the mammalian one. Building not only on studies in mammalian models but also in complementary model organisms, in this review we discuss (1) the mechanistic regulation of MiTF/TFE transcription factors; (2) their roles in different regions of the central nervous system, in different cell types, and their involvement in the development of neurodegenerative diseases, including lysosomal storage disorders; (3) the overlap and the compensation that occur among the different members of the family; (4) the importance of the evolutionary conservation of these protein and the process they regulate, which allows their study in different model organisms; and (5) their possible role as therapeutic targets in neurodegeneration.

show abstract

TFEB: A Emerging Regulator in Lipid Homeostasis for Atherosclerosis

Cited by 9 publications

References 119 publications

C. elegans orphan nuclear receptor NHR-42 represses innate immunity and promotes lipid loss downstream of HLH-30/TFEB

C. elegans orphan nuclear receptor NHR-42 represses innate immunity and promotes lipid loss downstream of HLH-30/TFEB

Transcription factor EB as a key molecular factor in human health and its implication in diseases

The Regulation of MiTF/TFE Transcription Factors Across Model Organisms: from Brain Physiology to Implication for Neurodegeneration

Contact Info

Product

Resources

About