Life Sciences & Biotechnology
Title : | Dissection of crosstalk between autophagy pathway and NRF2-axis during starvation |
Area of research : | Life Sciences & Biotechnology |
Principal Investigator : | Dr. Mayurbhai Sahani Himatbhai, M.S. University, Tamil Nadu |
Timeline Start Year : | 2023 |
Timeline End Year : | 2026 |
Contact info : | mayursa@yahoo.com |
Details
Executive Summary : | Autophagy is commonly studied in vitro, but it is not well understood in cell lines due to the complex molecular mechanisms involved in prolong starvation. This is particularly evident in neonates, host cells during bacterial and viral invasion, and neuronal cells due to stroke. Long-term nutrient stress is a hallmark in tumors due to lack of blood supply, leading to dynamic cellular and metabolic responses to adopt starvation. A study found that p62/SQSTM1 protein level was restored to basal level upon prolong starvation, which depends on NRF2. NRF2 and selected target genes of NRF2 are transcriptionally upregulated upon prolong starvation, eliciting cytoprotective roles by inducing the expression of detoxifying and antioxidant genes. However, the NRF2-axis is not reported to be involved in starvation-mediated autophagy. The proposed project aims to establish and evaluate the autophagy-NRF2 crosstalk, investigating whether transcriptional upregulation of NRF2 is autophagy dependent, whether NRF2 translocates to the nucleus, and whether autophagy and NRF2 are required for prolong starvation. The significance of studying autophagy and NRF2 cross talk during prolong starvation is crucial, as many cancers are "NRF2-addicted" and NRF2 inhibitors are under clinical trials. Preliminary unpublished data found upregulation of NRF2 without accumulation of p62 during prolong nutrient starvation in autophagy intact cells that mimic the core of tumor cells. Establishing a crosstalk between autophagy and NRF2-axis would open up a novel dimension to understanding this cellular response during physiological stress. |
Total Budget (INR): | 41,07,200 |
Organizations involved