Autophagy mediates degradation of cytoplasmic material through the lysosomes and inefficiencies in this homeostatic process result in devastating human diseases. A number of nanomaterials induce autophagy -  most likely as a response to the presence of what the cell perceives as foreign of aberrant material. Effective strategies aimed at enhancing cellular clearance, however, should not only activate autophagosome formation to compartmentalize toxic material, but also promote autophagosome clearance by the lysosomes. Evidence of co-regulated roles of lysosomes and autophagosomes emerged from the recent discovery of an overarching regulatory gene network (CLEAR, Coordinated Lysosomal Expression and Regulation) and its master regulator, the transcription factor EB (TFEB). We identified a number of nanomaterials that activate TFEB and enhance clearance and mapped autophagy induction in different in vitro systems with regard to nanoparticle size, composition, concentration and surface properties. This study will advance our understanding of the toxicological profile and therapeutic potential of nanoparticles.

Nanoparticles as autophagy activators

245th National Meeting (2013)

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