CoChat
Sign Up
Cited by 255Autophagy in Disease and TherapyCalcium signaling and nucleotide metabolismCellular transport and secretion

Transcriptional Regulation of Autophagy: Mechanisms and Diseases

Open access
Di Malta, Chiara, Cinque, Laura, Settembre, Carmine·2019·Frontiers in Cell and Developmental Biology
DOI 10.3389/fcell.2019.00114PMC PMC6614182
Open this paper in CoChat — free accountOpen PDF

Abstract

Macro (Autophagy) is a catabolic process that relies on the cooperative function of two organelles: the lysosome and the autophagosome. The recent discovery of a transcriptional gene network that co-regulates the biogenesis and function of these two organelles, and the identification of transcription factors, miRNAs and epigenetic regulators of autophagy, demonstrated that this catabolic process is controlled by both transcriptional and post-transcriptional mechanisms. In this review article, we discuss the nuclear events that control autophagy, focusing particularly on the role of the MiT/TFE transcription factor family. In addition, we will discuss evidence suggesting that the transcriptional regulation of autophagy could be targeted for the treatment of human genetic diseases, such as lysosomal storage disorders (LSDs) and neurodegeneration.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.3389/fcell.2019.00114

Cites

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Emerging evidence suggests that modulation of these targets is mostly coordinated by nuclear translocation of MiT/TFE family members including TFEB, TFE3, MITF, and TFEC.

    “Emerging evidence suggest that modulation of these targets is mostly coordinated by the nuclear translocation of members of the microphthalmia/transcription factor E (MiT/TFE) family that includes TFEB, TFE3, MITF, and TFEC [38].”

    From A gene toolbox for monitoring autophagy transcription (2021) · cites this paper as [38]

    In “TFEB and MiT Factors” (page unavailable), the paper says TFEB enters the nucleus and activates target genes, and that TFE3 and some MITF isoforms have regulated nuclear localization and roles in autophagy. It identifies TFEC as a MiT/TFE family member but does not establish that TFEC’s nuclear translocation coordinates regulation of these targets. The claim’s inclusion of TFEC in that mechanism is therefore unsupported. (LLM, conf=0.84)

    Experimental — accuracy not yet measured

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

The citation lists haven’t been fetched yet

References 131 · Cited by 255

Research works printed but not linked: 108

  1. Ahlberg J. Marzella L. Glaumann H. (1982). Uptake and degradation of proteins by isolated rat liver lysosomes. suggestion of a microautophagic pathway of proteolysis. Lab. Invest. 47 523– 532. 6755063
  2. Argani P. Antonescu C. R. Illei P. B. Lui M. Y. Timmons C. F. Newbury R. (2001). Primary renal neoplasms with the ASPL-TFE3 gene fusion of alveolar soft part sarcoma. Am. J. Pathol. 159 179– 192. 11438465 PMC1850400
  3. Artal-Martinez de Narvajas A. Gomez T. S. Zhang J.-S. Mann A. O. Taoda Y. Gorman J. A. (2013). Epigenetic regulation of autophagy by the methyltransferase G9a. Mol. Cell. Biol. 33 3983– 3993. 10.1128/MCB.00813-13 23918802 PMC3811684 · DOI
  4. Ballabio A. Gieselmann V. (2009). Lysosomal disorders: from storage to cellular damage. Biochim. Et Biophy. Acta 1793 684– 696. 10.1016/j.bbamcr.2008.12.001 19111581 · DOI · Paper page
  5. Bao J. Zheng L. Zhang Q. Li X. Zhang X. Li Z. (2016). Deacetylation of TFEB promotes fibrillar Aβ degradation by upregulating lysosomal biogenesis in microglia. Protein Cell 7 417– 433. 10.1007/s13238-016-0269-2 27209302 PMC4887328 · DOI
  6. Bartolomeo R. Cinque L. De Leonibus C. Forrester A. Salzano A. C. Monfregola J. (2017). MTORC1 hyperactivation arrests bone growth in lysosomal storage disorders by suppressing autophagy. J. Clin. Invest. 127 3717– 3729. 10.1172/JCI94130 28872463 PMC5617676 · DOI
  7. Beckmann H. Su L. K. Kadesch T. (1990). TFE3: a helix-loop-helix protein that activates transcription through the immunoglobulin enhancer MuE3 motif. Genes Dev. 4 167– 179. 2338243
  8. Calkin A. C. Tontonoz P. (2012). Transcriptional integration of metabolism by the nuclear sterol-activated receptors LXR and FXR. Nat. Rev. Mol. Cell Biol. 13 213– 224. 10.1038/nrm3312 22414897 PMC3597092 · DOI · Paper page
  9. Chantranupong L. Wolfson R. L. Orozco J. M. Saxton R. A. Scaria S. M. Bar-Peled L. (2014). The sestrins interact with GATOR2 to negatively regulate the amino-acid-sensing pathway upstream of MTORC1. Cell Rep. 9 1– 8. 10.1016/j.celrep.2014.09.014 25263562 PMC4223866 · DOI · Paper page
  10. Chauhan S. Ahmed Z. Bradfute S. B. Arko-Mensah J. Mandell M. A. Choi S. W. (2015). Pharmaceutical screen identifies novel target processes for activation of autophagy with a broad translational potential. Nat. Comm. 6: 8620. 10.1038/ncomms9620 26503418 PMC4624223 · DOI
  11. Chauhan S. Goodwin J. G. Chauhan S. Manyam G. Wang J. Kamat A. M. (2013). ZKSCAN3 is a master transcriptional repressor of autophagy. Mol. Cell 50 16– 28. 10.1016/j.molcel.2013.01.024 23434374 PMC3628091 · DOI
  12. Chen H. Fan M. Pfeffer L. M. Laribee R. N. (2012). The Histone H3 lysine 56 acetylation pathway is regulated by target of rapamycin (TOR) signaling and functions directly in ribosomal RNA biogenesis. Nucleic Acids Res. 40 6534– 6546. 10.1093/nar/gks345 22553361 PMC3413144 · DOI
  13. Cinque L. Forrester A. Bartolomeo R. Svelto M. Venditti R. Montefusco S. (2015). FGF signalling regulates bone growth through autophagy. Nature 528 272– 275. 10.1038/nature16063 26595272 · DOI · Paper page
  14. Comel A. Sorrentino G. Capaci V. Del Sal G. (2014). The cytoplasmic side of P53’s oncosuppressive activities. FEBS Lett. 588 2600– 2609. 10.1016/j.febslet.2014.04.015 24747877 · DOI
  15. Cortes C. J. Miranda H. C. Frankowski H. Batlevi Y. Young J. E. Le A. (2014). Polyglutamine-expanded androgen receptor interferes with TFEB to elicit autophagy defects in SBMA. Nat. Neurosci. 17 1180– 1189. 10.1038/nn.3787 25108912 PMC4180729 · DOI
  16. Cox T. M. Cachón-González M. B. (2012). The cellular pathology of lysosomal diseases. J. Pathol. 226 241– 254. 10.1002/path.3021 21990005 · DOI
  17. Decressac M. Mattsson B. Weikop P. Lundblad M. Jakobsson J. Björklund A. (2013). TFEB-mediated autophagy rescues midbrain dopamine neurons from α-synuclein toxicity. Proc. Natl. Acad. Sci. U.S.A. 110 E1817– E1826. 10.1073/pnas.1305623110 23610405 PMC3651458 · DOI · Paper page
  18. Dehay B. Bové J. Rodríguez-Muela N. Perier C. Recasens A. Boya P. (2010). Pathogenic lysosomal depletion in parkinson’s disease. J. Neurosci. 30 12535– 12544. 10.1523/JNEUROSCI.1920-10.2010 20844148 PMC6633458 · DOI · Paper page
  19. Deretic V. Singh S. Master S. Harris J. Roberts E. Kyei G. (2006). Mycobacterium tuberculosis inhibition of phagolysosome biogenesis and autophagy as a host defence mechanism. Cell. Microbiol. 8 719– 727. 10.1111/j.1462-5822.2006.00705.x 16611222 · DOI
  20. Di Malta C. Siciliano D. Calcagni A. Monfregola J. Punzi S. Pastore N. (2017). Transcriptional activation of RagD GTPase controls MTORC1 and promotes cancer growth. Science 356 1188– 1192. 10.1126/science.aag2553 28619945 PMC5730647 · DOI
  21. Ferron M. Settembre C. Shimazu J. Lacombe J. Kato S. Rawlings D. J. (2013). A RANKL-PKCβ-TFEB signaling cascade is necessary for lysosomal biogenesis in osteoclasts. Genes Dev. 27 955– 969. 10.1101/gad.213827.113 23599343 PMC3650231 · DOI
  22. Fu W. Ma Q. Chen L. Li P. Zhang M. Ramamoorthy S. (2009). MDM2 acts downstream of P53 as an E3 ligase to promote FOXO ubiquitination and degradation. J. Biol. Chem. 284 13987– 14000. 10.1074/jbc.M901758200 19321440 PMC2682847 · DOI
  23. Füllgrabe J. Ghislat G. Cho D. Rubinsztein D. C. (2016). Transcriptional regulation of mammalian autophagy at a glance. J Cell Sci. 129 3059– 3066. 10.1242/jcs.188920 27528206 · DOI
  24. Füllgrabe J. Lynch-Day M. A. Heldring N. Li W. Struijk R. B. Ma Q. (2013). The histone H4 lysine 16 acetyltransferase HMOF regulates the outcome of autophagy. Nature 500 468– 471. 10.1038/nature12313 23863932 PMC4006103 · DOI
  25. Gang H. Dhingra R. Wang Y. Mughal W. Gordon J. W. Kirshenbaum L. A. (2011). Epigenetic regulation of E2F-1-dependent Bnip3 transcription and cell death by nuclear factor-KB and histone deacetylase-1. Pediatr. Cardiol. 32 263– 266. 10.1007/s00246-011-9893-z 21293853 · DOI
  26. Green D. R. Kroemer G. (2009). Cytoplasmic functions of the tumour suppressor P53. Nature 458 1127– 1130. 10.1038/nature07986 19407794 PMC2814168 · DOI · Paper page
  27. Haq R. Fisher D. E. (2011). Biology and clinical relevance of the micropthalmia family of transcription factors in human cancer. J. Clin. Oncol. 29 3474– 3482. 10.1200/JCO.2010.32.6223 21670463 · DOI
  28. Hara T. Nakamura K. Matsui M. Yamamoto A. Nakahara Y. Suzuki-Migishima R. (2006). Suppression of basal autophagy in neural cells causes neurodegenerative disease in mice. Nature 441 885– 889. 10.1038/nature04724 16625204 · DOI · Paper page
  29. Harris H. Rubinsztein D. C. (2011). Control of autophagy as a therapy for neurodegenerative disease. Nat. Rev. Neurol. 8 108– 117. 10.1038/nrneurol.2011.200 22187000 · DOI
  30. He C. Klionsky D. J. (2009). Regulation mechanisms and signaling pathways of autophagy. Ann. Rev. Genet. 43 67– 93. 10.1146/annurev-genet-102808-114910 19653858 PMC2831538 · DOI · Paper page
  31. Hemesath T. J. Steingrímsson E. McGill G. Hansen M. J. Vaught J. Hodgkinson C. A. (1994). Microphthalmia, a critical factor in melanocyte development, defines a discrete transcription factor family. Genes Dev. 8 2770– 2780. 10.1101/gad.8.22.2770 7958932 · DOI · Paper page
  32. Hurley J. H. Schulman B. A. (2014). Atomistic autophagy: the structures of cellular self-digestion. Cell 157 300– 311. 10.1016/j.cell.2014.01.070 24725401 PMC4038036 · DOI
  33. Jeong E. Brady O. A. Martina J. A. Pirooznia M. Tunc I. Puertollano R. (2018). The transcription factors TFE3 and TFEB amplify P53 dependent transcriptional programs in response to DNA damage. ELife 7: e40856. 10.7554/eLife.40856 30520728 PMC6292694 · DOI
  34. Kauffman E. C. Ricketts C. J. Rais-Bahrami S. Yang Y. Merino M. J. Bottaro D. P. (2014). Molecular genetics and cellular features of TFE3 and TFEB fusion kidney cancers. Nat. Rev. Urol. 11 465– 475. 10.1038/nrurol.2014.162 25048860 PMC4551450 · DOI
  35. Kaur J. Debnath J. (2015). Autophagy at the crossroads of catabolism and anabolism. Nat. Rev. Mol Cell Biol. 16 461– 472. 10.1038/nrm4024 26177004 · DOI
  36. Kaushik S. Cuervo A. M. (2012). Chaperone-mediated autophagy: a unique way to enter the lysosome world. Trends Cell Biol. 22 407– 417. 10.1016/j.tcb.2012.05.006 22748206 PMC3408550 · DOI
  37. Kenzelmann Broz D. Spano Mello S. Bieging K. T. Jiang D. Dusek R. L. Brady C. A. (2013). Global genomic profiling reveals an extensive p53-regulated autophagy program contributing to key P53 responses. Genes Dev. 27 1016– 1031. 10.1101/gad.212282.112 23651856 PMC3656320 · DOI · Paper page
  38. Kilpatrick K. Zeng Y. Hancock T. Segatori L. (2015). Genetic and chemical activation of TFEB mediates clearance of aggregated α-Synuclein. PLoS One 10: e0120819. 10.1371/journal.pone.0120819 25790376 PMC4366176 · DOI
  39. Komatsu M. Waguri S. Chiba T. Murata S. Iwata J. Tanida I. (2006). Loss of autophagy in the central nervous system causes neurodegeneration in mice. Nature 441 880– 884. 10.1038/nature04723 16625205 · DOI · Paper page
  40. Kourmouli N. Jeppesen P. Mahadevhaiah S. Burgoyne P. Wu R. Gilbert D. M. (2004). Heterochromatin and tri-methylated lysine 20 of histone H4 in animals. J. Cell Sci. 117(Pt 12), 2491– 2501. 10.1242/jcs.01238 15128874 · DOI
  41. Lan F. Cacicedo J. M. Ruderman N. Ido Y. (2008). SIRT1 modulation of the acetylation status, cytosolic localization, and activity of LKB1. possible role in AMP-activated protein kinase activation. J. Biol. Chem. 283 27628– 27635. 10.1074/jbc.M805711200 18687677 PMC2562073 · DOI · Paper page
  42. Lapierre L. R. Kumsta C. Sandri M. Ballabio A. Hansen M. (2015). Transcriptional and epigenetic regulation of autophagy in aging. Autophagy 11 867– 880. 10.1080/15548627.2015.1034410 25836756 PMC4502732 · DOI
  43. Latifkar A. Ling L. Hingorani A. Johansen E. Clement A. Zhang X. (2019). Loss of sirtuin 1 alters the secretome of breast cancer cells by impairing lysosomal integrity. Dev. Cell 49 393.e– 408.e. 10.1016/j.devcel.2019.03.011 30982660 PMC6519475 · DOI
  44. Lawrence M. Daujat S. Schneider R. (2016). Lateral thinking: how histone modifications regulate gene expression. Trends Genet. 32 42– 56. 10.1016/j.tig.2015.10.007 26704082 · DOI
  45. Lee I. H. Cao L. Mostoslavsky R. Lombard D. B. Liu J. Bruns N. E. (2008). A role for the NAD-dependent deacetylase sirt1 in the regulation of autophagy. Proc. Natl. Acad. Sci. U.S.A. 105 3374– 3379. 10.1073/pnas.0712145105 18296641 PMC2265142 · DOI
  46. Lee J. M. Wagner M. Xiao R. Kim K. Feng D. Lazar M. A. (2014). Nutrient-sensing nuclear receptors coordinate autophagy. Nature 516 112– 115. 10.1038/nature13961 25383539 PMC4267857 · DOI
  47. Li L. Friedrichsen H. J. Andrews S. Picaud S. Volpon L. Ngeow K. (2018). A TFEB nuclear export signal integrates amino acid supply and glucose availability. Nat. Comm. 9: 2685. 10.1038/s41467-018-04849-7 29992949 PMC6041281 · DOI
  48. Li S. Song Y. Quach C. Guo H. Jang G.-B. Maazi H. (2019). Transcriptional regulation of autophagy-lysosomal function in BRAF-driven melanoma progression and chemoresistance. Nat. Comm. 10: 1693. 10.1038/s41467-019-09634-8 30979895 PMC6461621 · DOI
  49. Li Y. Xu M. Ding X. Yan C. Song Z. Chen L. (2016). Protein kinase C controls lysosome biogenesis independently of MTORC1. Nat. Cell Biol. 18 1065– 1077. 10.1038/ncb3407 27617930 · DOI
  50. Lin X.-X. Sen I. Janssens G. E. Zhou X. Fonslow B. R. Edgar D. (2018). DAF-16/FOXO and HLH-30/TFEB Function as combinatorial transcription factors to promote stress resistance and longevity. Nat. Comm. 9: 4400. 10.1038/s41467-018-06624-0 30353013 PMC6199276 · DOI
  51. Liu H.-Y. Han J. Cao S. Y. Hong T. Zhuo D. Shi J. (2009). Hepatic autophagy is suppressed in the presence of insulin resistance and hyperinsulinemia: inhibition of Foxo1-dependent expression of key autophagy genes by insulin. J. Biol. Chem. 284 31484– 31492. 10.1074/jbc.M109.033936 19758991 PMC2781544 · DOI
  52. Mammucari C. Milan G. Romanello V. Masiero E. Rudolf R. Del Piccolo P. (2007). FoxO3 controls autophagy in skeletal muscle in vivo. Cell Metab. 6 458– 471. 10.1016/j.cmet.2007.11.001 18054315 · DOI · Paper page
  53. Martina J. A. Chen Y. Gucek M. Puertollano R. (2012). MTORC1 functions as a transcriptional regulator of autophagy by preventing nuclear transport of TFEB. Autophagy 8 903– 914. 10.4161/auto.19653 22576015 PMC3427256 · DOI
  54. Martina J. A. Diab H. I. Lishu L. Jeong-A L. Patange S. Raben N. (2014). The nutrient-responsive transcription factor TFE3 promotes autophagy, lysosomal biogenesis, and clearance of cellular debris. Sci. Signal. 7: ra9. 10.1126/scisignal.2004754 24448649 PMC4696865 · DOI · Paper page
  55. Martina J. A. Puertollano R. (2018). Protein phosphatase 2A stimulates activation of TFEB and TFE3 transcription factors in response to oxidative stress. J. Biol. Chem. 293 12525– 12534. 10.1074/jbc.RA118.003471 29945972 PMC6093222 · DOI
  56. Medina D. L. Di Paola S. Peluso I. Armani A. De Stefani D. Venditti R. (2015). Lysosomal calcium signalling regulates autophagy through calcineurin and TFEB. Nat. Cell Biol. 17 288– 299. 10.1038/ncb3114 25720963 PMC4801004 · DOI
  57. Medina D. L. Fraldi A. Bouche V. Annunziata F. Mansueto G. Spampanato C. (2011). Transcriptional activation of lysosomal exocytosis promotes cellular clearance. Dev. Cell 21 421– 430. 10.1016/j.devcel.2011.07.016 21889421 PMC3173716 · DOI
  58. Menzies F. M. Fleming A. Rubinsztein D. C. (2015). Compromised autophagy and neurodegenerative diseases. Nat. Rev. Neurosci. 16 345– 357. 10.1038/nrn3961 25991442 · DOI · Paper page
  59. Mijaljica D. Prescott M. Devenish R. J. (2011). Microautophagy in mammalian cells: revisiting a 40-year-old conundrum. Autophagy 7 673– 682. 21646866
  60. Miyaguchi Y. Tsuchiya K. Sakamoto K. (2009). P53 negatively regulates the transcriptional activity of FOXO3a under oxidative stress. Cell Biol. Int. 33 853– 860. 10.1016/j.cellbi.2009.04.017 19427386 · DOI
  61. Mizushima N. Komatsu M. (2011). Autophagy: renovation of cells and tissues. Cell 147 728– 741. 10.1016/j.cell.2011.10.026 22078875 · DOI
  62. Mizushima N. Levine B. Cuervo A. M. Klionsky D. J. (2008). Autophagy fights disease through cellular self-digestion. Nature 451 1069– 1075. 10.1038/nature06639 18305538 PMC2670399 · DOI · Paper page
  63. Mizushima N. Yoshimori T. Ohsumi Y. (2011). The role of atg proteins in autophagosome formation. Ann. Rev. Cell Dev. Biol. 27 107– 132. 10.1146/annurev-cellbio-092910-154005 21801009 · DOI · Paper page
  64. Morselli E. Mariño G. Bennetzen M. V. Eisenberg T. Megalou E. Schroeder S. (2011). Spermidine and resveratrol induce autophagy by distinct pathways converging on the acetylproteome. J. Cell Biol. 192 615– 629. 10.1083/jcb.201008167 21339330 PMC3044119 · DOI
  65. Napolitano F. Carrella D. Mandriani B. Pisonero-Vaquero S. Sirci F. Medina D. L. (2018). Gene2drug: a computational tool for pathway-based rational drug repositioning. Bioinformatics 34 1498– 1505. 10.1093/bioinformatics/btx800 29236977 · DOI
  66. Napolitano G. Esposito A. Choi H. Matarese M. Benedetti V. Di Malta C. (2018). mTOR-dependent phosphorylation controls TFEB nuclear export. Nat. Comm. 9: 3312. 10.1038/s41467-018-05862-6 30120233 PMC6098152 · DOI
  67. Palmieri M. Impey S. Kang H. di Ronza A. Pelz C. Sardiello M. (2011). Characterization of the CLEAR network reveals an integrated control of cellular clearance pathways. Hum. Mol. Genet. 20 3852– 3866. 10.1093/hmg/ddr306 21752829 · DOI · Paper page
  68. Palmieri M. Pal R. Nelvagal H. R. Lotfi P. Stinnett G. R. Seymour M. L. (2017). MTORC1-independent TFEB activation via Akt inhibition promotes cellular clearance in neurodegenerative storage diseases. Nat. Comm. 8: 14338. 10.1038/ncomms14338 28165011 PMC5303831 · DOI
  69. Pan H. Yan Y. Liu C. Finkel T. (2017). The role of ZKSCAN3 in the transcriptional regulation of autophagy. Autophagy 13 1235– 1238. 10.1080/15548627.2017.1320635 28581889 PMC5529079 · DOI
  70. Pastore N. Blomenkamp K. Annunziata F. Piccolo P. Mithbaokar P. Maria Sepe R. (2013). Gene transfer of master autophagy regulator tfeb results in clearance of toxic protein and correction of hepatic disease in alpha-1-anti-trypsin deficiency. EMBO Mol. Med. 5 397– 412. 10.1002/emmm.201202046 23381957 PMC3598080 · DOI · Paper page
  71. Peña-Llopis S. Vega-Rubin-de-Celis S. Schwartz J. C. Wolff N. C. Tran T. A. Zou L. (2011). Regulation of TFEB and V-ATPases by MTORC1. EMBO J. 30 3242– 3258. 10.1038/emboj.2011.257 21804531 PMC3160667 · DOI
  72. Perera R. M. Di Malta C. Ballabio A. (2019). MiT/TFE family of transcription factors, lysosomes, and cancer. Ann. Rev. Cancer Biol. 3 203– 222. 10.1146/annurev-cancerbio-030518-055835 PMC6812561 31650096 · DOI
  73. Platt F. M. d’Azzo A. Davidson B. L. Neufeld E. F. Tifft C. J. (2018). Lysosomal storage diseases. Nat. Rev. Dis. Primers 4: 27. 10.1038/s41572-018-0025-24 30275469 · DOI
  74. Pogenberg V. Ogmundsdóttir M. H. Bergsteinsdóttir K. Schepsky A. Phung B. Deineko V. (2012). Restricted leucine zipper dimerization and specificity of DNA recognition of the melanocyte master regulator MITF. Genes Dev. 26 2647– 2658. 10.1101/gad.198192.112 23207919 PMC3521630 · DOI · Paper page
  75. Polager S. Ofir M. Ginsberg D. (2008). E2F1 regulates autophagy and the transcription of autophagy genes. Oncogene 27 4860– 4864. 10.1038/onc.2008.117 18408756 · DOI · Paper page
  76. Polito V. A. Li H. Martini-Stoica H. Wang B. Yang L. Xu Y. (2014). Selective clearance of aberrant tau proteins and rescue of neurotoxicity by transcription factor EB. EMBO Mol. Med. 6 1142– 1160. 10.15252/emmm.201303671 25069841 PMC4197862 · DOI
  77. Puertollano R. Ferguson S. M. Brugarolas J. Ballabio A. (2018). The complex relationship between TFEB transcription factor phosphorylation and subcellular localization. EMBO J. 37: e98804. 10.15252/embj.201798804 29764979 PMC5983138 · DOI
  78. Reddy K. Cusack C. L. Nnah I. C. Khayati K. Saqcena C. Huynh T. B. (2016). Dysregulation of nutrient sensing and clearance in presenilin deficiency. Cell Rep. 14 2166– 2179. 10.1016/j.celrep.2016.02.006 26923592 PMC4793148 · DOI
  79. Rega L. R. Polishchuk E. Montefusco S. Napolitano G. Tozzi G. Zhang J. (2016). Activation of the transcription factor EB rescues lysosomal abnormalities in cystinotic kidney cells. Kidney Int. 89 862– 873. 10.1016/j.kint.2015.12.045 26994576 · DOI
  80. Renault V. M. Thekkat P. U. Hoang K. L. White J. L. Brady C. A. Kenzelmann Broz D. (2011). The pro-longevity gene foxo3 is a direct target of the P53 tumor suppressor. Oncogene 30 3207– 3221. 10.1038/onc.2011.35 21423206 PMC3136551 · DOI
  81. Roczniak-Ferguson A. Petit C. S. Froehlich F. Qian S. Ky J. Angarola B. (2012). The transcription factor TFEB links MTORC1 signaling to transcriptional control of lysosome homeostasis. Sci. Signal. 5 ra42– ra42. 10.1126/scisignal.2002790 22692423 PMC3437338 · DOI
  82. Sahu R. Kaushik S. Clement C. C. Cannizzo E. S. Scharf B. Follenzi A. (2011). Microautophagy of cytosolic proteins by late endosomes. Dev. Cell 20 131– 139. 10.1016/j.devcel.2010.12.003 21238931 PMC3025279 · DOI · Paper page
  83. Saikia M. Wang X. Mao Y. Wan J. Pan T. Qian S.-B. (2016). Codon optimality controls differential MRNA translation during amino acid starvation. RNA 22 1719– 1727. 10.1261/rna.058180.116 27613579 PMC5066624 · DOI
  84. Sanchez A. M. Csibi A. Raibon A. Cornille K. Gay S. Bernardi H. (2012). AMPK promotes skeletal muscle autophagy through activation of forkhead FoxO3a and interaction with Ulk1. J. Cell. Biochem. 113 695– 710. 10.1002/jcb.23399 22006269 · DOI
  85. Sardiello M. Palmieri M. di Ronza A. Medina D. L. Valenza M. Gennarino V. A. (2009). A gene network regulating lysosomal biogenesis and function. Science 325 473– 477. 10.1126/science.1174447 19556463 · DOI · Paper page
  86. Sato S. Roberts K. Gambino G. Cook A. Kouzarides T. Goding C. R. (1997). CBP/P300 as a co-factor for the microphthalmia transcription factor. Oncogene 14 3083– 3092. 10.1038/sj.onc.1201298 9223672 · DOI
  87. Seok S. Fu T. Choi S.-E. Li Y. Zhu R. Kumar S. (2014). Transcriptional regulation of autophagy by an FXR-CREB axis. Nature 516 108– 111. 10.1038/nature13949 25383523 PMC4257899 · DOI
  88. Settembre C. De Cegli R. Mansueto G. Saha P. K. Vetrini F. Visvikis O. (2013). TFEB controls cellular lipid metabolism through a starvation-induced autoregulatory loop. Nat. Cell Biol. 15 647– 658. 10.1038/ncb2718 23604321 PMC3699877 · DOI · Paper page
  89. Settembre C. Zoncu R. Medina D. L. Vetrini F. Erdin S. Erdin S. (2012). A lysosome-to-nucleus signalling mechanism senses and regulates the lysosome via MTOR and TFEB: self-regulation of the lysosome via MTOR and TFEB. EMBO J. 31 1095– 1108. 10.1038/emboj.2012.32 22343943 PMC3298007 · DOI
  90. Shang L. Chen S. Du F. Li S. Zhao L. Wang X. (2011). Nutrient starvation elicits an acute autophagic response mediated by Ulk1 dephosphorylation and its subsequent dissociation from AMPK. Proc. Natl. Acad. Sci. U.S.A. 108 4788– 4793. 10.1073/pnas.1100844108 21383122 PMC3064373 · DOI
  91. Shaw J. Yurkova N. Zhang T. Gang H. Aguilar F. Weidman D. (2008). Antagonism of E2F-1 regulated Bnip3 transcription by NF-KappaB is essential for basal cell survival. Proc. Natl. Acad. Sci. U.S.A. 105 20734– 20739. 10.1073/pnas.0807735105 19088195 PMC2603431 · DOI
  92. Shin H.-J. Kim H. Oh S. Lee J.-G. Kee M. Ko H.-J. (2016). AMPK-SKP2-CARM1 signalling cascade in transcriptional regulation of autophagy. Nature 534 553– 557. 10.1038/nature18014 27309807 PMC5568428 · DOI
  93. Song W. Wang F. Savini M. Ake A. di Ronza A. Sardiello M. (2013). TFEB regulates lysosomal proteostasis. Hum. Mol. Genet. 22 1994– 2009. 10.1093/hmg/ddt052 23393155 · DOI · Paper page
  94. Spampanato C. Feeney E. Li L. Cardone M. Lim J.-A. Annunziata F. (2013). Transcription factor EB (TFEB) is a new therapeutic target for pompe disease. EMBO Mol. Med. 5 691– 706. 10.1002/emmm.201202176 23606558 PMC3662313 · DOI · Paper page
  95. Steingrimsson E. Tessarollo L. Pathak B. Hou L. Arnheiter H. Copeland N. G. (2002). Mitf and Tfe3, two members of the Mitf-Tfe family of BHLH-Zip transcription factors, have important but functionally redundant roles in osteoclast development. Proc. Natl. Acad. Sci. U.S.A. 99 4477– 4482. 10.1073/pnas.072071099 11930005 PMC123673 · DOI
  96. Tracy K. Dibling B. C. Spike B. T. Knabb J. R. Schumacker P. Macleod K. F. (2007). BNIP3 is an RB/E2F target gene required for hypoxia-induced autophagy. Mol. Cell. Biol. 27 6229– 6242. 10.1128/MCB.02246-2246 17576813 PMC1952167 · DOI
  97. Tsunemi T. Ashe T. D. Morrison B. E. Soriano K. R. Au J. Vázquez Roque R. A. (2012). PGC-1α rescues huntington’s disease proteotoxicity by preventing oxidative stress and promoting TFEB function. Sci. Transl. Med. 4: 142ra97. 10.1126/scitranslmed.3003799 22786682 PMC4096245 · DOI
  98. Vega-Rubin-de-Celis S. Peña-Llopis S. Konda M. Brugarolas J. (2017). Multistep regulation of TFEB by MTORC1. Autophagy 13 464– 472. 10.1080/15548627.2016.1271514 28055300 PMC5361595 · DOI
  99. Wang C. Niederstrasser H. Douglas P. M. Lin R. Jaramillo J. Li Y. (2017). Small-molecule TFEB pathway agonists that ameliorate metabolic syndrome in mice and extend C. elegans lifespan. Nat. Comm. 8: 2270. 10.1038/s41467-017-02332-3 29273768 PMC5741634 · DOI
  100. Webb A. E. Brunet A. (2014). FOXO transcription factors: key regulators of cellular quality control. Trends Biochem. Sci. 39 159– 169. 10.1016/j.tibs.2014.02.003 24630600 PMC4021867 · DOI
  101. Xiao Q. Yan P. Ma X. Liu H. Perez R. Zhu A. (2014). Enhancing astrocytic lysosome biogenesis facilitates Aβ clearance and attenuates amyloid plaque pathogenesis. J. Neurosci. 34 9607– 9620. 10.1523/JNEUROSCI.3788-13.2014 25031402 PMC4099542 · DOI · Paper page
  102. Xiao Q. Yan P. Ma X. Liu H. Perez R. Zhu A. (2015). Neuronal-targeted TFEB accelerates lysosomal degradation of APP, Reducing Aβ generation and amyloid plaque pathogenesis. J. Neurosci. 35 12137– 12151. 10.1523/JNEUROSCI.0705-15.2015 26338325 PMC4556784 · DOI
  103. Xiong X. Tao R. DePinho R. A. Dong X. C. (2012). The autophagy-related gene 14 (Atg14) is regulated by forkhead box O transcription factors and circadian rhythms and plays a critical role in hepatic autophagy and lipid metabolism. J. Biol. Chem. 287 39107– 39114. 10.1074/jbc.M112.412569 22992773 PMC3493951 · DOI
  104. Xu P. Das M. Reilly J. Davis R. J. (2011). JNK regulates FoxO-dependent autophagy in neurons. Genes Dev. 25 310– 322. 10.1101/gad.1984311 21325132 PMC3042155 · DOI
  105. You H. Jang Y. You-Ten A. I. Okada H. Liepa J. Wakeham A. (2004). P53-dependent inhibition of FKHRL1 in response to DNA damage through protein kinase SGK1. Proc. Natl. Acad. Sci. U.S.A. 101 14057– 14062. 10.1073/pnas.0406286101 15383658 PMC521120 · DOI
  106. Zhang J. Wang J. Xu J. Lu Y. Jiang J. Wang L. (2016). Curcumin targets the TFEB-lysosome pathway for induction of autophagy. Oncotarget 7 75659– 75671. 10.18632/oncotarget.12318 27689333 PMC5342768 · DOI
  107. Zhao J. Brault J. J. Schild A. Cao P. Sandri M. Schiaffino S. (2007). FoxO3 coordinately activates protein degradation by the autophagic/lysosomal and proteasomal pathways in atrophying muscle cells. Cell Metab. 6 472– 483. 10.1016/j.cmet.2007.11.004 18054316 · DOI · Paper page
  108. Zhao Y. Yang J. Liao W. Liu X. Zhang H. Wang S. (2010). Cytosolic FoxO1 is essential for the induction of autophagy and tumour suppressor activity. Nat. Cell Biol. 12 665– 675. 10.1038/ncb2069 20543840 · DOI

Authors
Di Malta, C., Cinque, L., & Settembre, C.
Affiliations
Telethon Institute Of Genetics And Medicine (IT)
ORCID
Venue
Frontiers in Cell and Developmental Biology
Publisher
Frontiers Media SA
Published
2019-07-02
Volume
7
Pages
114-114
ISSN
2296-634X (ISSN-L)
DOI
10.3389/fcell.2019.00114
PMC
PMC6614182
OpenAlex
W2948810228
Cited by
255
References
131
Citations by year
2026: 21 · 2025: 15 · 2024: 29 · 2023: 43 · 2022: 60 · 2021: 54 · 2020: 27 · 2019: 5
FWCI
5.33
Type
journal article
Language
en
Open access
Licence
Locations
  • Frontiers in Cell and Developmental Biology (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
Topics
  • Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Physiology › Calcium signaling and nucleotide metabolism
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
Keywords
autophagy, transcriptional regulation, lysosomes, autophagosomes, lysosomal storage disease, neurodegeneration, microRNA, epigenetic regulation, post-transcriptional regulation

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review