TRPML3 regulates expression of development-related neuronal genes, and augments starvation-induced autophagy mediated transcriptional regulation in HEK cells

Autophagy (self-eating) involves sorting of cargo like aggregated or misfolded proteins and damaged organelles, and their degradation via the endo-lysosomal system. It is a conserved process that is crucial in survival, cell stress response, and differentiation. Transient Receptor Potential Mucolipin-3 (TRPML3) is an endolysosomal calcium channel largely implicated in the mechanisms of endocytosis and autophagy. Overexpression and channel activation of TRPML3 has been reported to induce autophagy in cell-line models. However, its effect on the gene expression patterns, both before and during autophagy induction, is not clearly understood. Here, we have explored the changes in the transcriptomic profile of an in vitro serum starvation model of autophagy by RNA sequencing experiments in an over-expression background of TRPML3. We report that serum-starvation induced autophagy leads to downregulation of development-related neuronal genes and gene sets. TRPML3 overexpression during autophagy induction further amplifies the effect of starvation in downregulating neuronal gene sets. But, when nutrition is not a limiting condition, TRPML3 overexpression upregulates neuronal genes that promote development. In summary, overexpression of TRPML3 promotes neuronal development under ‘fed’ conditions, while significantly arresting development by augmenting the effects of starvation-induced autophagy in HEK293T cells.