title: The autophagic response to polystyrene nanoparticles is mediated by transcription factor EB and depends on surface charge.
abstract: BACKGROUND
  A number of engineered nanoparticles induce autophagy, the main catabolic pathway that regulates bulk degradation of cytoplasmic material by the lysosomes. Depending on the specific physico-chemical properties of the nanomaterial, however, nanoparticle-induced autophagy may have different effects on cell physiology, ranging from enhanced autophagic degradation to blockage of autophagic flux. To investigate the molecular mechanisms underlying the impact of nanoparticle charge on the nature of the autophagic response, we tested polystyrene nanoparticles (50 nm) with neutral, anionic, and cationic surface charges.
  
  
  RESULTS
  We found all polystyrene nanoparticles investigated in this study to activate autophagy. We showed that internalization of polystyrene nanoparticles results in activation of the transcription factor EB, a master regulator of autophagy and lysosome biogenesis. Autophagic clearance, however, was observed to depend specifically on the charge of the nanoparticles. Particularly, we found that the autophagic response to polystyrene nanoparticles presenting a neutral or anionic surface involves enhanced clearance of autophagic cargo. Cell exposure to polystyrene nanoparticles presenting a cationic surface, on the other hand, results in transcriptional upregulation of the pathway, but also causes lysosomal dysfunction, ultimately resulting in blockage of autophagic flux.
  
  
  CONCLUSIONS
  This study furthers our understanding of the molecular mechanisms that regulate the autophagic response to nanoparticles, thus contributing essential design criteria for engineering benign nanomaterials.
authors.affiliation: Department of Chemical and Biomolecular Engineering, Rice University, Houston, TX, 77005, USA. sws1983@gmail.com.
authors.forename: Wensi
authors.initials: W
authors.lastname: Song
authors.affiliation: Department of Chemical and Biomolecular Engineering, Rice University, Houston, TX, 77005, USA. lauren.b.popp@rice.edu.
authors.forename: Lauren
authors.initials: L
authors.lastname: Popp
authors.affiliation: Department of Chemical and Biomolecular Engineering, Rice University, Houston, TX, 77005, USA. jyang4444@gmail.com.
authors.forename: Justin
authors.initials: J
authors.lastname: Yang
authors.affiliation: Department of Chemical and Biomolecular Engineering, Rice University, Houston, TX, 77005, USA. ayushi2820@gmail.com.
authors.forename: Ayushi
authors.initials: A
authors.lastname: Kumar
authors.affiliation: Department of Chemical and Biomolecular Engineering, Rice University, Houston, TX, 77005, USA. varunshenoyg@rice.edu.
authors.forename: Varun Shenoy
authors.initials: VS
authors.lastname: Gangoli
authors.affiliation: Department of Chemical and Biomolecular Engineering, Rice University, Houston, TX, 77005, USA. segatori@rice.edu.|Department of Biochemistry and Cell Biology, Rice University, Houston, TX, 77005, USA. segatori@rice.edu.|Department of Bioengineering, Rice University, Houston, TX, 77005, USA. segatori@rice.edu.
authors.forename: Laura
authors.initials: L
authors.lastname: Segatori
mesh_terms: D000818:Animals; D001343:Autophagy / Q000187:drug effects* / Q000235:genetics; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / Q000235:genetics* / Q000378:metabolism; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D005347:Fibroblasts; D006367:HeLa Cells; D006801:Humans; D008055:Lipids / Q000096:biosynthesis / Q000235:genetics; D052119:Lysosomal-Associated Membrane Protein 2 / Q000235:genetics / Q000378:metabolism; D008247:Lysosomes / Q000187:drug effects* / Q000378:metabolism; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism; D053758:Nanoparticles / Q000737:chemistry*; D016716:PC12 Cells; D010316:Particle Size; D011137:Polystyrenes / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D055672:Static Electricity; D015533:Transcriptional Activation / Q000187:drug effects
chemical_list: D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; C497811:LAMP2 protein, human; D008055:Lipids; D052119:Lysosomal-Associated Membrane Protein 2; C477012:MAP1LC3A protein, human; D008869:Microtubule-Associated Proteins; D011137:Polystyrenes; C064972:TFEB protein, human; C051596:lipopigments