Autophagy and lysosomal dysfunction as emerging mechanisms of nanomaterial toxicity
Top Cited Papers
Open Access
- 1 January 2012
- journal article
- review article
- Published by Springer Science and Business Media LLC in Particle and Fibre Toxicology
- Vol. 9 (1), 20
- https://doi.org/10.1186/1743-8977-9-20
Abstract
The study of the potential risks associated with the manufacture, use, and disposal of nanoscale materials, and their mechanisms of toxicity, is important for the continued advancement of nanotechnology. Currently, the most widely accepted paradigms of nanomaterial toxicity are oxidative stress and inflammation, but the underlying mechanisms are poorly defined. This review will highlight the significance of autophagy and lysosomal dysfunction as emerging mechanisms of nanomaterial toxicity. Most endocytic routes of nanomaterial cell uptake converge upon the lysosome, making the lysosomal compartment the most common intracellular site of nanoparticle sequestration and degradation. In addition to the endo-lysosomal pathway, recent evidence suggests that some nanomaterials can also induce autophagy. Among the many physiological functions, the lysosome, by way of the autophagy (macroautophagy) pathway, degrades intracellular pathogens, and damaged organelles and proteins. Thus, autophagy induction by nanoparticles may be an attempt to degrade what is perceived by the cell as foreign or aberrant. While the autophagy and endo-lysosomal pathways have the potential to influence the disposition of nanomaterials, there is also a growing body of literature suggesting that biopersistent nanomaterials can, in turn, negatively impact these pathways. Indeed, there is ample evidence that biopersistent nanomaterials can cause autophagy and lysosomal dysfunctions resulting in toxicological consequences.Keywords
This publication has 129 references indexed in Scilit:
- Manganese nanoparticle activates mitochondrial dependent apoptotic signaling and autophagy in dopaminergic neuronal cellsToxicology and Applied Pharmacology, 2011
- Silica nanoconstruct cellular toleration threshold in vitroJournal of Controlled Release, 2011
- Endocytosis of titanium dioxide nanoparticles in prostate cancer PC-3M cellsNanomedicine: Nanotechnology, Biology and Medicine, 2011
- Fullerenol cytotoxicity in kidney cells is associated with cytoskeleton disruption, autophagic vacuole accumulation, and mitochondrial dysfunctionToxicology and Applied Pharmacology, 2010
- Endocytosis of nanomedicinesJournal of Controlled Release, 2010
- Autophagy: assays and artifactsThe Journal of Pathology, 2010
- Autophagy Inhibition Compromises Degradation of Ubiquitin-Proteasome Pathway SubstratesMolecular Cell, 2009
- The role of oxidative stress in ambient particulate matter-induced lung diseases and its implications in the toxicity of engineered nanoparticlesFree Radical Biology & Medicine, 2008
- Endocytic mechanisms for targeted drug deliveryAdvanced Drug Delivery Reviews, 2007
- Eating Oneself and Uninvited Guests: Autophagy-Related Pathways in Cellular DefenseCell, 2005