LA JOLLA (August 29, 2025)—In a groundbreaking study, researchers at the Salk Institute have unveiled a new dimension in cellular biology, revealing the critical role of microproteins in maintaining mitochondrial function and addressing metabolic disorders. The study, published in Science Advances, focuses on a microprotein named SLC35A4-MP, discovered last year, which is crucial for mitochondrial structure and metabolic stress regulation in mouse fat cells.
This discovery could pave the way for innovative treatments targeting obesity, aging, and other mitochondrial-related diseases. The research highlights the underestimated significance of these small proteins, which were once considered mere genetic anomalies.
The Role of Microproteins in Mitochondrial Function
Mitochondria, often referred to as the powerhouses of the cell, are essential for energy production. The Salk Institute’s research suggests that microproteins like SLC35A4-MP play a vital role in preserving mitochondrial integrity and function. “Microproteins have long been dismissed as random genetic junk,” says Alan Saghatelian, senior author and professor at Salk. “Our work adds to a growing body of research demonstrating that many of them are actually crucial regulators of cell physiology.”
The discovery of SLC35A4-MP’s genetic code in an upstream open reading frame on a strand of mRNA marked a significant shift in understanding protein synthesis. Traditionally, it was believed that each mRNA strand codes for a single protein. However, advancements in genetic sequencing have revealed that these upstream open reading frames can code for functional microproteins.
Experimental Insights and Implications
The study conducted by Saghatelian’s lab involved removing SLC35A4-MP from mouse brown fat cells, which are metabolically active and regulate energy balance and body temperature. When exposed to cold or a high-fat diet, mice lacking SLC35A4-MP showed compromised mitochondrial function, leading to structural damage and inflammation.
These findings underscore the fundamental role of SLC35A4-MP in regulating brown fat cell function and response to metabolic stress. The implications extend beyond brown fat, suggesting potential therapeutic targets for a range of metabolic and mitochondrial disorders.
Expert Opinions and Future Directions
Andréa Rocha, the study’s first author, emphasizes the importance of these findings. “SLC35A4-MP regulates mitochondrial function and lipid metabolism in mice, which really goes to show that microproteins cannot be overlooked as we search for biological factors that regulate health,” she states.
As microprotein research gains momentum, the potential for discovering more functional microproteins is vast. Saghatelian hopes this study will fuel further exploration into the physiological relevance of microproteins. “Our study says yes, they are important physiological regulators,” he asserts.
Support and Collaborations
The research was a collaborative effort involving multiple institutions and was supported by various grants, including those from the National Institutes of Health and the National Science Foundation. The study’s co-authors hail from esteemed organizations such as UC San Diego, Rockefeller University, and Novartis Research Foundation.
The Salk Institute, founded by Jonas Salk, continues to push the boundaries of scientific knowledge, with this study marking another milestone in its mission to unlock the secrets of life.
As the field of microprotein research blossoms, the potential for breakthroughs in understanding and treating metabolic disorders grows ever brighter. With each discovery, the scientific community moves closer to unraveling the complexities of cellular life and its impact on human health.
