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Cellular and Molecular Life Sciences

, Volume 71, Issue 13, pp 2483–2497 | Cite as

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

  • José A. Martina
  • Heba I. Diab
  • Huiqing Li
  • Rosa PuertollanoEmail author
Review

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.

Keywords

MITF TFE3 TFEB Autophagy Lysosomes Nutrients Transcription Disease 

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

Notes

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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Copyright information

© Springer Basel (outside the USA) 2014

Authors and Affiliations

  • José A. Martina
    • 1
  • Heba I. Diab
    • 1
  • Huiqing Li
    • 1
  • Rosa Puertollano
    • 1
    Email author
  1. 1.Cell Biology and Physiology Center, National Heart, Lung, and Blood InstituteNational Institutes of HealthBethesdaUSA

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