KAUST reveals the secrets of acid stress and its relationship to disease

A pioneering scientific achievement from King Abdullah University of Science and Technology

In a significant scientific breakthrough, a research team from King Abdullah University of Science and Technology (KAUST) precise molecular mechanisms explaining how human cells respond to acidic stress, a condition common in many serious diseases such as cancer and chronic inflammation. The results of this pioneering study, published in the prestigious journal Communications Biology, offer a deeper understanding of how acidic environments affect cellular function and open new avenues for developing innovative therapeutic strategies.

Scientific context: What is acid stress and its importance?

Acid stress, or tissue acidification, is defined as a decrease in the pH of the environment surrounding cells. Although the human body maintains a delicate pH balance, this balance can be disrupted under certain pathological conditions. For example, cancerous tumors produce large amounts of lactic acid, creating an acidic environment that promotes their growth and spread. This phenomenon is also associated with chronic inflammation and age-related biological processes, but its direct impact on cellular mechanisms remains incompletely understood.

The study focuses on two vital components within the cell: mitochondria, which act as “power plants,” and the molecule NAD⁺, an essential cofactor involved in hundreds of metabolic reactions and energy production. Any disruption to these two components can lead to serious cellular disorders.

Study results: Revealing the relationship between acidity and energy imbalance

Using a sophisticated bioreactor system that allows for precise control of the cell's environmental conditions, KAUST researchers have shown that even a slight increase in acidity leads to significant disruption of energy production mechanisms. They found that acidic stress causes a sharp depletion of levels of the vital molecule NAD⁺. This depletion, in turn, impairs mitochondrial function and triggers a cascade of stress responses within the cell, disrupting its normal functions.

Most importantly, the study demonstrated that this damage is not permanent. By supplementing stressed cells with nicotinamide mononucleotide (NMN), a precursor to NAD⁺, researchers were able to partially restore NAD⁺ levels, leading to improved cell health and restored metabolic functions. Professor Mo Li, a co-author of the study, said, “Our findings highlight acidity as a major contributing factor in disease development and open the door to potential strategies for cell protection and supporting human health.”.

Importance and expected effects: From laboratory to clinic

The importance of this study extends beyond the boundaries of research laboratories, as it carries promising implications at the local and international levels.

• At the local level: This research enhances the position of the Kingdom of Saudi Arabia and KAUST as a leading global center for innovation and scientific research, in line with the ambitious goals of Vision 2030 to build a knowledge-based economy.
• At the international level, the findings provide a fundamental understanding of a common mechanism in widespread diseases. Identifying NAD⁺ depletion as a link between acid stress and cellular dysfunction could lead to the development of novel therapies targeting this pathway, not only for cancer and inflammation, but also for age-related diseases. This places the research at the forefront of global efforts to combat chronic diseases and extend healthy lifespan.

Dr. Saman Al-Salimi, one of the researchers involved, confirms that these results indicate that acidity is not just a byproduct of the disease, but rather an active factor driving cellular dysfunction, thus opening up new avenues for future therapeutic intervention.