Cellular Traffic Control System Regulates Nutrient Sensing and Energy Balance

Scientists at Ben-Gurion University of the Negev have uncovered a remarkable mechanism by which human cells actively monitor nutrient levels and maintain energy homeostasis. This sophisticated process involves a synchronized traffic control system at the cellular surface, where transporter proteins such as the liver citrate transporter (NaCT) and glucose transporters (Glut) work in unison. Instead of relying solely on slower internal sensing methods, cells employ these transporters to continuously and rapidly assess external nutrient availability, adjusting uptake within minutes to ensure energy balance and regulate blood sugar.

This discovery challenges previous assumptions that cellular responses to nutrients are slow and inefficient. Instead, this new understanding reveals that transporter proteins are key players in a dynamic and coordinated system that actively manages metabolic processes. When nutrients like glucose or citrate are scarce, transporter activity increases to compensate. Conversely, when nutrients become abundant, uptake levels normalize swiftly, preventing metabolic imbalance.

The research highlights a specific molecular region in NaCT, called the H4c domain, which facilitates this tight coordination between transporters. Altering this interaction can influence blood glucose levels, as demonstrated in experiments where disruption of NaCT led to decreased blood sugar in mice. Such insights open new possibilities for treating metabolic conditions like diabetes and cancer.

Prof. Ehud Ohana and Ph.D. student Noa Yehoshua led the study, recently published in Nature Communications. Their findings suggest that by targeting the synchronized functions of these transporter systems, new therapeutic strategies could be developed to improve metabolic health. For example, enhancing the activity of NaCT could help diabetic patients better regulate blood sugar levels, providing a promising path toward more effective treatments.

Furthermore, the implications extend beyond diabetes. Cancer cells often manipulate glucose and citrate transporters to fuel their rapid growth. The researchers have engineered molecules that reprogram tumor cell metabolism by interacting with these transporters, showing potential for anti-cancer therapies. This approach aims to selectively eradicate tumor cells while sparing healthy tissue, a significant step forward in metabolic disease treatment.

Overall, this groundbreaking research reveals that cells use a highly coordinated, molecularly synchronized system to sense and respond to nutrient changes swiftly. This discovery paves the way for developing innovative drugs that manipulate cellular transporter interactions to manage and potentially cure metabolic diseases and cancer.