Auxin-dependent modulation of the Unfolded Protein Response in Caenorhabditis elegans.

Abstract

The Proteostasis network, through a coordinated action of an intricate intracellular signalling network, serves to maintain a state of balanced proteome referred to as protein homeostasis or proteostasis. Endoplasmic Reticulum (ER) is responsible for proper folding and assembly of almost one-third of all secreted and membrane proteins thus contributing to maintaining cellular and organismal proteostasis. However, perturbations due to genetic or environmental factors can disrupt ER homeostasis and cause the accumulation of misfolded proteins in the ER lumen (ER stress). To cope up with the burden of misfolded proteins in its lumen, the ER upregulates a set of conserved and highly specific intracellular signal transduction pathways collectively known as the Unfolded Protein Response (UPR). The UPR is characterized by the induction of protein folding chaperones, degradation of irreversibly misfolded proteins, protein translation attenuation and activation of apoptosis under prolonged ER stress. A decline in proteostasis is one of the hallmarks of aging and is a major cause for many age-related diseases such as neurodegenerative, cardiovascular, and others. My findings indicate that the plant hormone, indole acetic acid commonly known as auxin, can modulate the UPR in the nematode Caenorhabditis elegans, providing resistance to ER stress. In my thesis work, I have shown that auxin provides tolerance against ER stress by upregulating the transcription of some of the well-established UPR target genes via the IRE-1/XBP-1 branch of the UPR. Since auxin is an indole derivative and indoles have recently been shown to promote organismal healthspan, my results point to the auxin-dependent activation of the UPR as a mechanism to improve healthspan.