TABLE 1.
Summary of functions and cellular processes associated with MiT/TFE proteins.
| Protein | Functions | Processes | References |
| C. elegans | |||
| HLH-30 | Transcriptional response to oxidative, thermal, and proteotoxic stress and regulation of detoxifying enzyme expression. | Survival and life span extension. | Kenyon, 2010; Leiser et al., 2015; Bennett et al., 2017; Kumsta et al., 2017; Lee and Mylonakis, 2017; Lin et al., 2018; Liu et al., 2020 |
| Upregulation of SKN-1. | Increase in mitochondrial biogenesis. | Mansueto et al., 2017; Palikaras et al., 2017 | |
| Regulation of lysosomal lipases and vitellogenins, response to glucose exposure. | Lipid mobilization and homeostasis, metabolic adaptation in response to food availability, cell death. | O’Rourke and Ruvkun, 2013; Harvald et al., 2017; Palikaras et al., 2017; Murphy et al., 2019 | |
| Regulation of immune and auto-lysosomal gene upregulation, xenography. | S. aureus and Gram-positive bacterial infection. | Visvikis et al., 2014; Najibi et al., 2016; Chen H. D. et al., 2017; El-Houjeiri et al., 2019; Li et al., 2019 | |
| Adult reproductive quiescence. | Life span extension. | Gerisch et al., 2020 | |
| Protein aggregate formation. | Aging and neurodegeneration. | Kim et al., 2016; Butler et al., 2019 | |
| Upregulation of autophagy and lysosomal genes. | Longevity. | Lapierre et al., 2013; Nakamura et al., 2016; Lin et al., 2018; Silvestrini et al., 2018; Liu et al., 2020 | |
| D. melanogaster | |||
| Mitf | Autophagosome biogenesis and endo-lysosomal compartment. | Wing disk tissue formation. | Tognon et al., 2016 |
| Activation of autophagy and increase in lysosomal activity. | Decrease in lipid droplet size. | Bouche et al., 2016 | |
| Upregulation by lysosomal dysfunction and autophagy block. | Compensatory mechanism in a Gaucher disease model. | Kinghorn et al., 2016 | |
| D. rerio | |||
| Tfeb | Notochord vacuole formation. | Vertebra development. | Ellis et al., 2013; Sun et al., 2020 |
| Expansion of lysosomal compartment. | Microglial cells. | Gan et al., 2019 | |
| Repression of myelinization in oligodendrocytes. | Neurodegeneration. | Meireles et al., 2018 | |
| Mammals | |||
| TFEB/TFE3 | Upregulation of genes involved in lysosomal biogenesis and autophagy. | Nutrient deprivation. | Sardiello and Ballabio, 2009; Sardiello et al., 2009; Settembre et al., 2011, 2012; Martina et al., 2012, 2014b; Roczniak-Ferguson et al., 2012; Martina and Puertollano, 2013; Medina et al., 2015 |
| TFEB inactivation by CRM1/Exportin-1. | Nutrient replenishment. | Napolitano et al., 2018 | |
| Regulation at transcriptional level, autoregulatory-feedback loop and proteasomal degradation by STUB1. | Autoregulation. | Settembre et al., 2013; Ghosh et al., 2015; Sha et al., 2017 | |
| Upregulation of lysosomal, autophagy or apoptotic genes induced by oxidative stress, ER stress, mitochondrial dysfunction or genotoxic stress. mTORC1-dependent and -independent mechanism. | Response to different stress conditions. | Medina et al., 2011; Palmieri et al., 2011; Settembre et al., 2011; Spampanato et al., 2013; Martina et al., 2014b, 2016; Zhang et al., 2016; Fernandez-Mosquera et al., 2017; Leow et al., 2017; Brady et al., 2018a; Martina and Puertollano, 2018; Pisonero-Vaquero et al., 2020; Zhang et al., 2020 | |
| Induction of mitochondrial biogenesis and mitophagy. | Mitochondria biogenesis and quality control. | Settembre et al., 2013; Nezich et al., 2015; Salma et al., 2015; Mansueto et al., 2017; Erlich et al., 2018; Kim et al., 2018; Contreras et al., 2020; Popov, 2020 | |
| Lipophagy and lipolysis induction. Obesity prevention and reversal. | Lipid catabolism. | Settembre et al., 2013; Emanuel et al., 2014; Pastore et al., 2017 | |
| Glycogen synthesis and hyperglycemia reduction. | Transcriptional control of the insulin pathway and glucose metabolism. | Nakagawa et al., 2006; Iwasaki et al., 2012; Salma et al., 2015; Mansueto et al., 2017; Pastore et al., 2017 | |
| Adipose tissue regulation. Induction or reduction of WAT browning, autophagy and lipolysis. | Regulation of whole-body metabolism. | Fujimoto et al., 2013; Wada et al., 2016; Chen L. et al., 2017; Evans et al., 2019; Huber et al., 2019 | |
| Upregulation of lysosomal genes, cytokines and inflammatory genes. | Pathogenic infection and immune response. | Visvikis et al., 2014; Campbell et al., 2015; Najibi et al., 2016; Ouimet et al., 2016; Pastore et al., 2016; Nabar and Kehrl, 2017; Wu et al., 2017; Brady et al., 2018b; Singh et al., 2018; El-Houjeiri et al., 2019; Li et al., 2019; Irazoqui, 2020 | |
| TFE3 gain-of-function induces developmental syndrome. | Development. | Villegas et al., 2019; Diaz et al., 2020 | |
| Mammals | |||
| TFEB/TFE3 | Reduction of stem cell differentiation by induction of a quiescent state | Stem cell differentiation | Betschinger et al., 2013; Young et al., 2016; Hu et al., 2020; Kobayashi et al., 2019 |
| Myelinization repression | Neurodegeneration | Meireles et al., 2018 | |
| Regulation of cell cycle transition and proliferation | Cell cycle | Malumbres and Barbacid, 2009; Young et al., 2016; Doronzo et al., 2019; Kobayashi et al., 2019; Pastore et al., 2020; Pisonero-Vaquero et al., 2020; Yin et al., 2020 | |
| Involvement in pancreatic adenocarcinomas, renal carcinoma development, cellular migration, and tumorigenesis | Cancer | Levy et al., 2006; Kauffman et al., 2014; Giatromanolaki et al., 2015; Perera et al., 2015, 2019; Calcagni et al., 2016; Raben and Puertollano, 2016; Bretou et al., 2017; Di Malta et al., 2017; Sakamoto et al., 2018; Doronzo et al., 2019; Eichner et al., 2019; Wylie et al., 2019 | |
| MITF | Regulation of expression of genes involved in eye differentiation, epidermis pigmented cells, and deafness | Development | Hallsson et al., 2004; Curran et al., 2010; Liu et al., 2010; Goding and Arnheiter, 2019 |
CRM1, chromosomal maintenance 1; ER, endoplasmic reticulum; HLH-30, helix-loop-helix transcription factor 30; mTORC1, mammalian target of rapamycin complex 1; SKN-1, skinhead 1; STUB1, STIP1 homology and U-box-containing protein 1; WAT, white adipose tissue.