Professor Alan Sagatelyan discovers mitochondrial microprotein SLC35A4-MP — a new path to obesity and aging therapies

Researchers from the Salk Institute have identified a new microprotein structure, named SLC35A4-MP, which plays a key role in maintaining mitochondrial structure and regulating metabolic stress in fat cells in mice.

This work, published in Science Advances, is part of a series of studies from the institute highlighting the functional importance of microproteins in cell biology, metabolism, and stress response.

It was previously believed that each mRNA encodes only one protein. However, scientists have discovered that certain regions of mRNA, known as upstream open reading frames (uORFs), contained hidden codes for microproteins — previously thought to be “junk” or mere regulatory elements. Advances in sequencing and genetic analysis technologies have revised this view, showing that these fragments can in fact encode functional proteins.

SLC35A4-MP was first identified by Professor Alan Sagatelyan and, in 2024, found in the membranes of mitochondria. This suggested that it could be involved in maintaining the cell’s metabolic stability.

To confirm the functional significance of this microprotein, its role was studied in living organisms — in mice. The findings revealed that SLC35A4-MP regulates mitochondrial activity and lipid metabolism, especially in brown adipose (thermogenic) tissue. When this protein was removed, mitochondria in brown fat cells of mice lost their structural integrity, became enlarged and dysfunctional, and triggered inflammatory processes. This impaired the body’s ability to adapt to cold exposure or a high-fat diet.

The authors emphasize that since mitochondria are present in all types of cells, SLC35A4-MP could become a powerful therapeutic target for a range of conditions associated with metabolic and mitochondrial dysfunction — from obesity to aging processes and other diseases.

Follow NEWS.am Medicine on Facebook and Twitter