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Novel roles for the MiTF/TFE family of transcription factors in organelle biogenesis, nutrient sensing, and energy homeostasis

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Abstract

The MiTF/TFE family of basic helix–loop–helix leucine zipper transcription factors includes MITF, TFEB, TFE3, and TFEC. The involvement of some family members in the development and proliferation of specific cell types, such as mast cells, osteoclasts, and melanocytes, is well established. Notably, recent evidence suggests that the MiTF/TFE family plays a critical role in organelle biogenesis, nutrient sensing, and energy metabolism. The MiTF/TFE family is also implicated in human disease. Mutations or aberrant expression of most MiTF/TFE family members has been linked to different types of cancer. At the same time, they have recently emerged as novel and very promising targets for the treatment of neurological and lysosomal diseases. The characterization of this fascinating family of transcription factors is greatly expanding our understanding of how cells synchronize environmental signals, such as nutrient availability, with gene expression, energy production, and cellular homeostasis.

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Abbreviations

AKT:

v-akt murine thymoma viral oncogene

ARPE-19:

Retinal pigmented epithelium cell line

ASPL:

Alveolar soft part sarcoma chromosome region, candidate 1

ASPS:

Alveolar soft part sarcoma

ATF1:

Activating transcription factor 1

ATG1:

unc-51-like autophagy activating kinase 1

ATG13:

Autophagy-related 13

ATG16L:

Autophagy-related 16-like (S. cerevisiae)

ATG9B:

Autophagy-related 9B

ATP6V:

ATPase, H+ transporting, lysosomal

BCL2:

B-cell CLL/lymphoma 2

bHLH-LZ:

Basic/helix–loop–helix/leucine zipper

c-MET:

Receptor tyrosine kinase

C. elegans :

Caenorhabditis elegans

CCS:

Clear cell sarcoma

CDK2:

Cyclin-dependent kinase 2

CLEAR:

Coordinated lysosomal expression and regulation

CLTC:

Clathrin, heavy chain (Hc)

ERK2:

Mitogen-activated protein kinase 1

FOXO3:

Forkhead box O3

GAGs:

Glycosaminoglycans

GLUT4:

Solute carrier family 2 (facilitated glucose transporter, member 4)

GSK3β:

Glycogen synthase kinase 3 beta

GYS:

Glycogen synthase

HD:

Huntington’s disease

HIF1:

Hypoxia inducible factor 1

HK2:

Hexokinase 2

HLH-30:

Caenorhabditis elegans TFEB orthologue

HPS4:

Hermansky–Pudlak syndrome 4

IRF3:

Interferon regulatory factor 3

IRF7:

Interferon regulatory factor 7

IRS2:

Insulin receptor substrate 2

ISGs:

Interferon-stimulated genes

LAMP1:

Lysosomal-associated membrane protein 1

LROs:

Lysosome-related organelles

LSDs:

Lysosomal storage disorders

LYST:

Lysosomal trafficking regulator

MAP1LC3B:

Microtubule-associated protein 1 light chain 3 beta

MAX:

MYC-associated factor X

MCOLN1:

Mucolipin 1

MITF:

Microphthalmia-associated transcription factor

MPS-IIIA:

Mucopolysaccharidosis type IIIA

MSD:

Multiple sulfatase deficiency

MTORC1:

Mechanistic target of rapamycin (serine/threonine kinase) complex 1

MYC:

v-myc avian myelocytomatosis viral oncogene homolog

NONO:

Non-POU domain-containing, octamer-binding

NSCs:

Neuronal stem cells

p16:

Cyclin-dependent kinase inhibitor 2A

p21:

Cyclin-dependent kinase inhibitor 1A (p21, Cip1)

PD:

Parkinson’s disease

RCC:

Renal cell carcinoma

PI3K:

Phosphatidylinositol-4,5-bisphosphate 3-kinase

PPARA:

Peroxisome proliferator-activated receptor alpha

PPARGC1A:

Peroxisome proliferator-activated receptor gamma, coactivator 1 alpha

PRCC:

Papillary renal cell carcinoma (translocation-associated)

PKCβ:

Protein kinase C, beta

PSEN2:

Presenilin 2 (Alzheimer disease 4)

PSF:

Splicing factor proline/glutamine-rich

RANKL:

Tumor necrosis factor (ligand) superfamily, member 11

RHEB:

Ras homolog enriched in brain

SCAP:

SREBF chaperone

SNP:

Single nucleotide polymorphism

SQSTM1:

Sequestosome 1

SREBP:

Sterol regulatory element-binding protein

STING:

Stimulator of interferon genes

TBK1:

TANK-binding kinase 1

TFE3:

Transcription factor binding to IGHM enhancer 3

TFEB:

Transcription factor EB

TFEC:

Transcription factor EC

P53:

Tumor protein p53

tRCC:

Translocation renal cell carcinoma

TREX1:

Three prime repair exonuclease 1

TSC2:

Tuberous sclerosis 2

USF:

Upstream transcription factor

UVRAG:

UV radiation resistance associated

VPS11:

Vacuolar protein sorting 11 homolog (S. cerevisiae)

VPS18:

Vacuolar protein sorting 18 homolog (S. cerevisiae)

WIPI1:

WD repeat domain, phosphoinositide interacting 1

ZKSCAN3:

Zinc finger with KRAB and SCAN domains 3

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Acknowledgment

This work was supported by the Intramural Research Program of the National Institutes of Health, National Heart, Lung, and Blood Institute (NHLBI).

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  1. Cell Biology and Physiology Center, National Heart, Lung, and Blood Institute, National Institutes of Health, 9000 Rockville Pike, Bldg. 50/3537, Bethesda, MD, 20892, USA

    José A. Martina, Heba I. Diab, Huiqing Li & Rosa Puertollano

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  1. José A. Martina
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  2. Heba I. Diab
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  3. Huiqing Li
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  4. Rosa Puertollano
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Correspondence to Rosa Puertollano.

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J. A. Martina and H. I. Diab contributed equally to this work.

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Martina, J.A., Diab, H.I., Li, H. et al. Novel roles for the MiTF/TFE family of transcription factors in organelle biogenesis, nutrient sensing, and energy homeostasis. Cell. Mol. Life Sci. 71, 2483–2497 (2014). https://doi.org/10.1007/s00018-014-1565-8

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