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.
Highlights
Autophagy is an evolutionary conserved catabolic process devoted to the degradation of intracellular components
This review aims to summarize the “nuclear” control of autophagy, focusing in particular on the co-regulation of autophagy and lysosome biogenesis by the transcription factor EB (TFEB)
Binding to DNA is mediated by the recognition of a common DNA hexanucleotide sequence (CACGTG) known as the E-box (Hemesath et al, 1994). This sequence conforms to the canonical CANNTG motif, recognized by other bHLH-Zip transcription factors, specific nucleotide residues that flank this motif characterize the coordinated lysosomal expression and regulation (CLEAR) motif (GTCACGTGAC) that is preferentially recognized by microphthalmia/ transcription factor E (MiT/TFE) members (Sardiello et al, 2009; Palmieri et al, 2011; Martina et al, 2014)
Summary
Autophagy is an evolutionary conserved catabolic process devoted to the degradation of intracellular components. The modulation of autophagy in the maintenance of cellular homeostasis goes far beyond the response to nutrient fluctuation, as cells exploit autophagy to eliminate damaged organelles, misfolded proteins, and invading organisms (Deretic et al, 2006; Mizushima et al, 2008) Deregulation of these autophagy-dependent cytoprotective functions has been associated to different pathologies, including immune disorders, neurodegenerative diseases, cancer and aging (Deretic et al, 2006; Hara et al, 2006; Komatsu et al, 2006; Harris and Rubinsztein, 2011; Mizushima and Komatsu, 2011; White, 2015). This review aims to summarize the “nuclear” control of autophagy, focusing in particular on the co-regulation of autophagy and lysosome biogenesis by the transcription factor EB (TFEB)
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
