Autophagy: A Janus-Faced Role in Inflammation and Cancer
Hygeia.J.D.Med.6(2) 2014; 71-91.
Mohannad A. Elkhider and Bob Chaudhuri
De Montfort University, The Gateway, Leicester, LE1 9BH United Kingdom
Plan: This review focus on the role of autophagy, in up regulation, in the innate and adaptive immune response, in controlling carcinogenesis, and in supporting neuronal cell growth, development & remodeling. Also the review covers the therapeutic interventions involved in the cancer management through autophagy modulations.
Preface: Autophagy is a cellular degradative pathway where un wanted and weary cytosolic components are recycled. Any defects interfering with theintegrity of the autophagic machinery would compromises the cells defensesleaving the cell susceptible to infection by circulating pathogens. Currentliterature points out that the dysregulation of autophagy may be associatedwith the genesis of cancer. Accumulation of aberrant organelles and proteinsincreases the chances of triggering an inflammatory microenvironment favoringchromosomal instability and mutagenesis. The aggregation of certain proteinsyields cellular toxicity which eventually leads to cell death andneurodegeneration. Therefore, the autophagic duty of continuously monitoringand clearing out aggregated proteins isindispensable in neuronal cells.
Outcome: The accumulation of autophagosomes is an established assurance in a number of neuro degenerative diseases. However, this observation has triggered controversy whereas one opinion considers the activated autophagic pathway to act as an executioner by initiating neuronal cell death while the other explains the presence of autophagosomes as a final attempt by the cell to sustain viability against the increasing amount of stress.
Keywords: Autophagy,Cancer, Inflammation
Received:16 June 2014, Revised: 30 July 2014, Accepted: 25 August 2014, Available online: 10 October 2014
Mohannad A. Elkhider and Bob Chaudhuri. Autophagy: A Janus-faced role in inflammation and cancer. Hygeia.J.D.Med 2014; 6(2):57-77.Available from http://www.hygeiajournal.com / Article ID-Hygeia.J.D.Med/137/14. doi:10.15254/H.J.D.Med.6.2014.137.
Mohannad A. Elkhider, DeMont fort University; the Gateway, Leicester,LE1 9BH United Kingdom
Different modes of autophagy
A. Microautophagy mediates direct internalisation of organelles and cytosolic material by the lysosome.
B. Macroautophagy is hired for degrading larger components since it’s the most efficient amongst the three inbulk degradation. A double membrane vesicle, the autophagosome, engulfs the targeted protein/organelle aimed for degradation, once fully sequestered the autophagosome along with the substrate is delivered to the lysosome where the cargo is released.
C. Chaperone-mediated autophagy is unique for being the most selective form of degradation. Targeted substrates existing solely in the cytosol bind to autophagic chaperone via a special recognition motif. The chaperone /substrate complex then travels towards the lysosome and binds with lysosomal receptor in a manner independent of any membrane sequestration steps.