A new study published in Cell Press Blue, featuring researchers from the CU Anschutz Health and Wellness Center, provides important insights into how mitochondrial dysfunction affects the human energy expenditure, physical activity, and fatigue.
Researchers from Columbia University compared 10 adults with mitochondrial disease to 10 healthy adults and identified three key findings:
Higher energy demands: Individuals with mitochondrial disease expended approximately 195 additional calories per day under controlled laboratory conditions, even while moving less. In particular, elevated energy expenditure was observed during sleep.
Reduced activity may offset higher energy costs: Despite these increased energy demands, total daily energy expenditure was similar between groups during everyday life. Individuals with mitochondrial disease were approximately 39% less physically active, suggesting that reduced activity may help compensate for higher underlying energy costs.
A potential link to fatigue: Levels of GDF15, a protein associated with mitochondrial stress, were nearly five times higher in individuals with mitochondrial disease and were associated with greater fatigue, higher energy demands, and reduced physical activity.
Seth Creasy, PhD, and Edward Melanson, PhD, FACSM, contributed to this collaborative research by performing the free-living energy expenditure analyses using the doubly labeled water (DLW) method, a gold-standard technique for measuring how many calories individuals burn during their normal daily routines. Their work was critical in demonstrating that increased energy demands observed in the laboratory were not reflected in higher total daily energy expenditure under real-world conditions.
These findings highlight the importance of understanding not just how much energy the body expends, but how energy demands influence physical activity, fatigue, and overall metabolic health.
Read the publication: Context-specific hypermetabolism in humans with mitochondrial defects, Cell Press Blue (2026).