A recent article in Nature challenges the common belief that mitochondrial diseases are caused simply by a lack of energy (ATP). New research suggests that problems with how our cells produce energy lead to stress in the body, which uses up more energy than usual. This constant energy drain causes the problems seen in mitochondrial diseases. The authors emphasize the need for more studies to understand this process and how it affects the whole body, not just the cells.
Summary: in people with OxPhos defects, their bodies tend to use more energy than normal. This is partly due to a stress response that increases the production of certain molecules, like GDF15 and FGF21, which make the body burn more energy. However, using too much energy in this way can cause damage over time, leading to faster aging and health problems. This might explain why people with these defects feel tired, develop various health issues, and have shorter lifespans.
Current treatments for mitochondrial diseases mainly focus on managing symptoms, like using supplements for energy production or looking for future gene therapies. However, if hypermetabolism is a key factor in these diseases, it could open new ways to treat patients.
The researchers suggest exploring three possible treatment approaches:
Sleep: Many patients struggle with sleep, and napping may be their way of coping with high energy use. Improving sleep could help reduce their energy expenditure.
Psychological and behavioral therapies: Stress increases energy use, but practices like yoga and meditation can reduce energy expenditure. These approaches might help manage stress and improve patients' resilience.
Molecular therapies: Targeting certain stress responses or energy-regulating molecules like GDF15 and FGF21 could help reduce hypermetabolism and slow disease progression.
This article is a follow-up on the previous research on a psycho/physiological stress and mitochondrial function: Picard, M., McEwen, B.S. Psychological Stress and Mitochondria: A Systematic Review. Psychosom Med. 2018 Feb/Mar;80(2):141-153. doi: 10.1097/PSY.0000000000000545.
References:
Sturm, G., Karan, K.R., Monzel, A.S. et al. OxPhos defects cause hypermetabolism and reduce lifespan in cells and in patients with mitochondrial diseases. Commun Biol 6, 22 (2023). https://doi.org/10.1038/s42003-022-04303-x
Sercel, A., Sturm, G., Gallagher, D., St-Onge, M., Kempes, C., Pontzer, H., Hirano, M., Picard, M. Hypermetabolism and energetic constraints in mitochondrial disorders. Nat Metab. 2024 Feb;6(2):192-195. doi: 10.1038/s42255-023-00968-8.