The autophagic response to polystyrene nanoparticles is mediated by transcription factor EB and depends on surface charge

Journal of Nanobiotechnology

Research

Lauren Popp¹  Ayushi Kumar¹  Varun Shenoy Gangoli¹  Justin Yang¹  Wensi Song¹  Laura Segatori² 

[1] Department of Chemical and Biomolecular Engineering, Rice University, 77005, Houston, TX, USA;Department of Chemical and Biomolecular Engineering, Rice University, 77005, Houston, TX, USA;Department of Biochemistry and Cell Biology, Rice University, 77005, Houston, TX, USA;Department of Bioengineering, Rice University, 77005, Houston, TX, USA;

关键词: Autophagy;    Lipopigment;    Lysosome;    Nanoparticle;    Transcription factor EB (TFEB);   

DOI  :  10.1186/s12951-015-0149-6

 received in 2015-09-11, accepted in 2015-11-13,  发布年份 2015

来源: Springer

【 摘 要 】

BackgroundA 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.ResultsWe 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.ConclusionsThis study furthers our understanding of the molecular mechanisms that regulate the autophagic response to nanoparticles, thus contributing essential design criteria for engineering benign nanomaterials.

【 授权许可】

CC BY   
© Song et al. 2015