Review articleAutophagy: The spotlight for cellular stress responses
Graphical abstract
Section snippets
Presenting autophagy
In order to maintain a continuous protein turnover, there exists a constitutive proteasomal degradation system of proteins within the cell. But the system is known to be restricted to short-lived proteins present in the cell. Surprisingly, most of the cellular components are long lived. Therefore there must be an alternative recycling mechanism for the degradation of these macromolecules to promote adaptation and cell survival under adverse conditions. And autophagy was known to be very
The autophagy machinery
The whole mechanism of autophagy takes place in a well-known series of steps (Fig. 1) namely, Autophagosome formation, Selection of cargo, Autophagolysosome formation and Degradation. All these steps are very crucial for the autophagy process to take place successfully. Disruption of both earlier and later stages would equally affect the entire mechanism.
NF-κB links autophagy and inflammation
Mutations in the autophagy related genes were observed in inflammatory disease like Crohn's disease and other inflammation associated metabolic diseases [128]. During inflammation, there occurs an over expression of NF-κB (nuclear factor κ-light-chain-enhancer of activated B cells) at the inflamed sites which is induced by the transcription of pro-inflammatory genes to produce cytokines like TNFα and IL-1 [121]. Under normal condition, cells inactivate IKK, a major regulator of NF-κB to prevent
The ZKSCAN3-TFEB rival in autophagy regulation
ZKSCAN3 (Zinc finger protein with KRAB and SCAN domains 3) is a DNA-binding protein belonging to the zinc-finger family. It is involved in the transcriptional regulation of autophagy in that it represses the autophagy transcriptionally. Mounting evidences suggest that proteins functioning in autophagy (encoded by more than 60 genes) are transcriptionally modulated by ZKSCAN3. Under normal conditions, ZKSCAN3 localizes in the nucleus. In contrast, autophagy induction has led to the localization
Autophagy and cancer
Most of the autophagy regulators are oncogenes and tumor suppressors. And this is the reason behind the yet unknown role of autophagy in cancer [127]. A cell needs to undergo a change in the metabolic machinery to become cancerous. Autophagy is found to be down regulated in carcinogenesis. Cancer cells express a set of anti-autophagic genes like Bcl-2, AKT and PI3KC1 which makes it clear that autophagy serves as a hindrance for a normal cell in getting transformed into a cancerous one. Now the
Autophagy modulators at a glance
Recently, the development of autophagy modulators has become interests of many researchers to contribute to the better understanding of autophagy mechanism. Such research findings gave rise to effective modulators that are being successful in various stages of clinical trials.
Conclusion
Autophagy serves as a pro-survival mechanism for a cell in many cases. The process of autophagy is regulated by many regulators in vivo. And the integration of autophagy in different stress responses completely relies on the transcription factors that regulate the autophagy players functionally. The transcriptional factors like NF-κB are involved in multiple pathways and serve as better targets to target multiple signaling molecules via them. However, targeting the molecule in a functionally
Conflict of interest
The authors declare no conflict of interest.
Acknowledgements
The authors greatly acknowledge DST-SERB for the financial support through the Research Grant-SB/EMEQ-223/2014.
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