The Regulation Of Fatty Acid Metabolism By The NHR-14/HNF 4aplha Transcription Factor In Caenorhabditis Elegans.

Abstract

Energy production through metabolic reactions is essential for life in all organisms. Proper metabolic regulation strongly influences aging, as disruptions in these reactions can impair cellular homeostasis and stress response pathways. Lipid metabolism is a central metabolic process that contributes to energy balance and cellular function; however, disturbances in lipid regulatory pathways can increase susceptibility to oxidative damage and negatively affect organismal health and longevity. Accordingly, many organisms have evolved transcriptional regulators that coordinate metabolic activity with stress resistance. Our lab uses Caenorhabditis elegans to study the role of SKN-1/Nrf2 and its protective functions in conjunction with other, yet unknown, transcription factors. We have previously shown that transcription factors can influence stress resistance through detoxification gene regulation. I focused on the transcription factor NHR-14 and its role in oxidative stress responses. RNA-seq analysis of the nhr-14(tm1473) deletion showed downregulation of multiple fatty acid degradation genes, suggesting that NHR-14 functions as a positive regulator of metabolic pathways. I found that the mutation in the nhr-14(tm1473) gene resulted in decreased survival under oxidative stress, reduced brood size, and shortened lifespan. My investigation of NHR-14’s function, along with characterization of its role as a positive regulator, provides new understanding into the mechanisms that maintain stress resistance and highlights important implications for longevity.