Autophagy: The spotlight for cellular stress responses

Abstract

Autophagy is an essential cellular mechanism which plays "housekeeping" role in normal physiological processes including removing of long lived, aggregated and misfolded proteins, clearing damaged organelles, growth regulation and aging. Autophagy is also involved in a variety of biological functions like development, cellular differentiation, defense against pathogens and nutritional starvation. The integration of autophagy into these biological functions and other stress responses is determined by the transcriptional factors that undertake the regulatory mechanism. This review discusses the machinery of autophagy, the molecular web that connects autophagy to various stress responses like inflammation, hypoxia, ER stress, and various other pathologic conditions. Defects in autophagy regulation play a central role in number of diseases, including neurodegenerative diseases, cancer, pathogen infection and metabolic diseases. Similarly, inhibiting autophagy would contribute in the treatment of cancer. However, understanding the biology of autophagy regulation requires pharmacologically active compounds which modulate the autophagy process. Inducers of autophagy are currently receiving considerable attention as autophagy upregulation may be a therapeutic benefit for certain neurodegenerative diseases (via removal of protein aggregates) while the inhibitors are being investigated for the treatment of cancers. Both induction and inhibition of autophagy have been proven to be beneficial in the treatment of cancer. This dual role of autophagy in cancers is now getting uncovered by the advancement in the research findings and development of effective autophagy modulators.

Keywords: Apoptosis; Autophagy; Cancer; HIFα; Inflammation; NF-KB; Neurodegenerative diseases; Stress responses.