Researchers have uncovered a tiny but powerful protein that helps keep our cells’ energy factories humming – a discovery that could spark new approaches to tackling obesity and age-related decline. Scientists at the Salk Institute in La Jolla found that a “microprotein” in mouse fat cells plays a critical role in maintaining healthy mitochondria, the structures that generate energy in our cells. By preserving mitochondrial function, this diminutive protein helps cells burn fuel efficiently, which in turn could influence body weight and the aging process. The findings shine light on how molecular biology connects to everyday health, opening the door to science-backed strategies for better metabolismand longevity.
Mature brown fat cells from a mouse, with the newly discovered microprotein shown in red inside mitochondria (green) and nuclei in blue. This tiny protein helps preserve mitochondrial health under stress. (Credit: Salk Institute)
Mighty Mitochondria in Every Cell: Often dubbed the “powerhouses of the cell,” mitochondria convert the food we eat into usable energy. They are especially active in brown fat – a type of body fat that burns calories to produce heat and regulate body temperature. (Most fat tissue is white fat, which primarily stores energy.) When activated, brown fat can break down sugars and fats to warm us up, a process that also consumes excess nutrients. In fact, research supported by the NIH has shown that cold temperatures stimulate brown fat to soak up and burn fuel molecules, potentially protecting against obesity and diabetes by clearing fats and sugars from the bloodstream. Most of our daily activities, from walking up stairs to thinking, rely on mitochondria working properly. But if mitochondria falter, cells can’t use energy well – and that can contribute to common health issues. Studies have linked mitochondrial dysfunction to metabolic disorders (like obesity and type 2 diabetes) and even the aging process itself, since our cells become less efficient as we get older.
Microproteins: Hidden Regulators of Health: The term “microprotein” refers to a protein so small that scientists historically overlooked it. Our genes encode many large proteins, but embedded within some genes are tiny open reading frames that can produce microproteins – miniature proteins just a few dozen amino acids long. For years, these microproteins were dismissed as genetic “junk” or background noise. However, cutting-edge genomics has started to reveal that many microproteins do exist and have important jobs. “Microproteins have long been dismissed as random genetic junk, but our work shows that many are actually crucial regulators of cell physiology,” explains Alan Saghatelian, PhD, a professor at the Salk Institute and senior author of the new study. In recent years, scientists have identified microproteins involved in metabolism, stress responses, and other vital cellular functions. This represents a paradigm shift – even tiny proteins can wield big influence in biology. (The importance of metabolism in health is highlighted in resources like The Secret Life of Fat by biochemist Sylvia Tara, which explains how our fat tissue – including energy-burning brown fat – acts as an active organ, not just passive padding.)
A New Guardian of Metabolic Health: In the Salk Institute study, researchers focused on a microprotein named SLC35A4-MP, which they discovered hidden in the genetic code of a cell’s messenger RNA in 2024. This microprotein resides within the membranes of mitochondria in brown fat cells. To figure out what SLC35A4-MP does, the team conducted experiments in mice. Dr. Andréa L. Rocha, the study’s first author and a postdoctoral researcher in Saghatelian’s lab, helped engineer mice that lacked the gene for this microprotein specifically in their brown fat tissue. The result? Without SLC35A4-MP, the mice’s brown fat cells struggled mightily when put under stress.
The researchers exposed these mice to cold temperatures and a high-fat diet – two challenges that normally make brown fat ramp up its energy-burning metabolism. But mice missing the microprotein could not boost their metabolism in the cold. Their mitochondria became abnormally enlarged, structurally damaged, and inflamed. “We found that SLC35A4-MP regulates mitochondrial function and lipid metabolism in mice,” says Dr. Rocha, “which shows that microproteins cannot be overlooked as we search for factors that regulate health.” In other words, this tiny protein acted like a guardian for the cell’s powerhouses. Without it, not only did the mitochondria break down, but the brown fat cells showed signs of metabolic decline similar to what is seen in obesity – including cellular stress and inflammation. These issues in turn can lead to poorer energy burning and weight gain. The discovery of SLC35A4-MP’s role means scientists have identified a new leverage point in the cell’s machinery that keeps metabolism running smoothly.
Why It Matters – Fighting Obesity and Aging: Obesity and aging are two massive challenges for public health worldwide. According to the World Health Organization, as of 2022 about 43% of adults were overweight and 16% were obese – a prevalence that has more than doubled since 1990. Excess body fat raises the risk of heart disease, diabetes, and other problems. At the same time, our society is getting older: by 2030, 1 in 6 people on the planet will be over 60 years old. Aging is associated with a slowdown in metabolism and a decline in mitochondrial function, contributing to fatigue, muscle loss, and increased susceptibility to chronic diseases. Finding ways to improve mitochondrial health is therefore a priority for extending healthy lifespan. (For a deeper dive into the science of aging, Harvard geneticist David A. Sinclair’s book Lifespan: Why We Age—and Why We Don’t Have To explores cutting-edge insights on how we might slow aging at the cellular level.)
The new discovery of microprotein SLC35A4-MP is exciting because it points to a novel target for interventions. If a small protein can have such a big effect on metabolic fitness in cells, future therapies might be designed to boost its activity – or mimic its effects – in people. “This microprotein is preserving mitochondrial structure and function in brown fat, which is key for maintaining body temperature and energy balance,” notes Dr. Saghatelian. Enhancing mitochondrial resilience could potentially help treat metabolic disorders like obesity, or even mitigate aspects of aging. Of course, it’s early-stage research (done in mice), so any human applications will require much more study. Yet the principle is promising: by leveraging the body’s own tiny molecular tools, we might improve health in ways traditional approaches haven’t achieved. Importantly, this study adds to growing evidence that microproteins in general are an untapped wellspring of biological insight. “Our study says yes, microproteins are important physiological regulators,” Dr. Saghatelian emphasizes. He hopes these findings “add more fuel to the study of microproteins” – suggesting that many more helpful microproteins remain to be discovered for various conditions.
Everyday Health Implications: While scientists work on translating these findings into therapies, there are already practical steps we can take to support our mitochondrial and metabolic health. Decades of public health research have shown that lifestyle factors profoundly influence how well our metabolism functions:
Stay Active: Regular physical activity is one of the best ways to boost your mitochondria. Health agencies like the CDC recommend at least 150 minutes of moderate exercise per week (such as brisk walking) for adults. Exercise encourages your cells to produce more mitochondria and improves the efficiency of existing ones. This helps your body burn calories and may ward off metabolic problems – in fact, being active lowers the risk of developing type 2 diabetes and metabolic syndrome.
Eat a Balanced, Nutritious Diet: What we eat provides the raw materials for our mitochondria. Emphasize whole foods – vegetables, fruits, lean proteins, whole grains, and healthy fats – which contain vitamins and antioxidants that support cell function. Avoid excessive intake of sugary or ultra-processed foods that can contribute to weight gain and inflammation. A moderate calorie intake aligned with your energy needs helps prevent overloading your mitochondria.
Prioritize Sleep and Manage Stress: Poor sleep and chronic stress can disrupt hormones and metabolism. Aim for 7–9 hours of quality sleep per night, and use stress-reduction techniques (like mindfulness or exercise) to keep stress hormones in check. Good sleep and lower stress levels enable mitochondria and other systems to repair and operate optimally, aiding in weight management and healthy aging.
Engage Your Brown Fat (Sensibly): Brown fat is stimulated by cold exposure – that’s why you shiver in a chilly room as brown fat burns fuel to make heat. Some research suggests that safely exposing yourself to cool temperatures (for example, taking a brisk walk on a cool day or a brief cold shower if approved by your doctor) might activate brown fat and slightly boost metabolism. While this isn’t a weight loss cure-all, it highlights how our environment can tweak our biology. Always practice caution and moderation with cold exposure.
By minding these everyday habits, you can help keep your cellular “engines” in shape. As science advances, we may eventually have new tools – like microprotein-based medications – to further enhance metabolic health. It’s intriguing to imagine a future treatment that, say, increases the levels or activity of a beneficial microprotein like SLC35A4-MP to combat obesity or energize aging cells. Entire books have been written about the central role of mitochondria in health and disease (for instance, Mitochondria and the Future of Medicine by Dr. Lee Know illustrates how mitochondrial dysfunction underlies many chronic illnesses). This new research adds a valuable piece to that puzzle by showing that preserving mitochondrial integrity – even through a tiny protein – can have big effects.
Looking Ahead: The discovery of SLC35A4-MP is part of a broader scientific movement toward understanding how small players in our cells affect the bigger picture of health. What other microproteins might be quietly influencing processes like appetite, muscle strength, or brain aging? Uncovering those could open entirely new avenues for preventing disease. The Salk Institute team is optimistic, noting that microprotein research is “springing to life” after years of being underestimated.
For now, this study offers a hopeful message: even the tiniest components of our biology can be harnessed to improve well-being. By blending insights from molecular biology with practical health measures, we move closer to a future where obesity, diabetes, and perhaps certain aspects of aging become more manageable. It’s a potent reminder that in science – as in health – sometimes small changes can make a big difference.
Helpful resources:
1. Power, sex, and suicide: Mitochondria and meaning of life.
2. MG Mitochondrial Supplements with ATP, Vitamins, CoQ10 & PQQ.