IDENTIFICATION OF KEY REGULATORS IN CELLULAR METABOLIC HOMEOSTASIS

Abstract

Cellular metabolic homeostasis is a highly regulated phenomenon that is necessary to maintain homeostasis of energy, cell integrity, and survival in different physiological conditions. Malfunction of metabolic pathways has been closely linked to the development of various disorders such as cancer, diabetes and metabolic syndromes. The current work will determine the main molecular regulators that can keep the cellular metabolism at homeostasis and learn about the coordinated actions of these molecules in response to the stress.

A mix of biochemical and molecular methods was used, which consisted of metabolic tests, ATP quantification, glucose uptake, and reactive oxygen species (ROS) tests, as well as genomic and proteomic expression data of genes and proteins via RT-qPCR and Western blotting assays. The key metabolic regulators, such as AMP-activated protein kinase (AMPK), mechanistic target of rapamycin (mTOR), sirtuin 1 (SIRT1), and peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1 4 ), were analyzed.

The findings showed that metabolic stress causes a large discrepancy in cellular energy status, which is manifested by a decrease in ATP levels, changes in glucose metabolism, and oxidative stress. This imbalance was linked to the activation of AMPK signaling and repression of mTOR-mediated growth pathways, in addition to the regulation of SIRT1 and PGC-1A expression, showing a complex regulatory mechanism that re-established metabolic balance. The long-term stress levels led to the transition of adaptive metabolic regulation to the apoptotic signaling and the importance of setting a critical threshold beyond which the homeostasis becomes impossible. On the whole, the results indicate that the cellular metabolic stability is controlled by a network of interconnected regulatory signals and key signaling molecules. Knowledge of these regulatory systems has valuable information on the pathogenesis of illnesses and has provided other potential therapeutic control points in metabolic disorders.