It has been well established that a key transcription factor, HIF1-Alpha, is the master regulator when it comes to cellular adaptations induced by hypoxia (low oxygen levels). Its transcriptional role has been the focus of many research papers as its ability to upregulate glycolysis-related genes in oxygen-deprived environments has been observed in not only native mammalian cells but also in cancer cells. HIF1-Aplha is the major contributor to the tumor’s ability to shift its metabolism to an anaerobic one. This metabolic shift is known as the Warburg effect. Besides its transcriptional role, however, it has been hypothesized that HIF1-Alpha also has a non-transcriptional role in enhancing glycolysis in oxygen-starved cells. An increasing amount of evidence from the proposed host lab suggests that HIF1-Alpha helps to assemble so-called ‘glycolytic complexes’ or ‘metabolons’, significantly increasing anaerobic metabolism’s efficiency. These structures have been identified in prokaryotes, archaea, yeast, fungi, and mammalian cells and have significant implications for cell function in health and disease. However, the formation and function of these complexes in mammalian cells remain unclear. Therefore, this project aims to study the glycolytic metabolon in live mammalian cells under normoxic and hypoxic conditions using a state-of-the-art live cell imaging microscope. The current hypothesis is that these complexes play a major part in mammalian cell adaptations to hypoxic conditions by increasing the interactions between different parts of the machinery that drives glycolysis. The objective of the project is to visualize, localize, and quantify these glycolytic metabolons in live mammalian intestinal epithelial cells over a range of oxygen concentrations. The research is expected to establish a clearer sense of these complexes’ role in cellular adaptations to hypoxia. This knowledge could have very powerful applications in cancer research, as anaerobic metabolism is a major energy source for cancerous cells.
