Elevated Energy Production in Chronic Fatigue Syndrome Patients
Nick Lawson,1 Chung-Han Hsieh,1 Dana March,2 and Xinnan Wang1,*
Author information
1- Department of Neurosurgery, Stanford University School of Medicine, Stanford, CA, USA
2- Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, NY, USA
Abstract
Chronic Fatigue Syndrome (CFS) is a debilitating disease characterized by physical and mental exhaustion. The underlying pathogenesis is unknown, but impairments in certain mitochondrial functions have been found in some CFS patients. To thoroughly reveal mitochondrial deficiencies in CFS patients, here we examine the key aspects of mitochondrial function in blood cells from a paired CFS patient-control series. Surprisingly, we discover that in patients the ATP levels are higher and mitochondrial cristae are more condensed compared to their paired controls, while the mitochondrial crista length, mitochondrial size, shape, density, membrane potential, and enzymatic activities of the complexes in the electron transport chain remain intact. We further show that the increased ATP largely comes from non-mitochondrial sources. Our results indicate that the fatigue symptom in this cohort of patients is unlikely caused by lack of ATP and severe mitochondrial malfunction. On the contrary, it might be linked to a pathological mechanism by which more ATP is produced by non-mitochondrial sources.
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Discussion
CFS afflicts millions of people, but its underlying cause remains elusive. In this study, by examining mitochondrial phenotypes in depth in a patient-control series, we have revealed that there is no major mitochondrial defect in CFS patients. Despite finding that mitochondrial cristae are more condensed, the mitochondrial morphology, the ETC, and the ΔΨ remain intact in CFS patients compared to their paired controls. Intriguingly, we have shown that ATP production is stimulated in CFS patients, and the elevated ATP content mainly comes from non-mitochondrial sources. Our results present an unorthodox view on CFS pathology: the fatigue is not caused by lack of ATP, and instead might be caused by a pathological process linked to non-mitochondrial ATP production such as glycolysis25.
Mitochondrial crista architecture is exquisitely and dynamically maintained to support the changing mitochondrial aerobic respiratory rate26–30. The membrane area and number of cristae are expanded upon energy need elevation to promote respiratory activities31,32. The fact that the crista number is increased in CFS patients suggests that their energy demands might be unusually high, which triggers condensation of mitochondrial crista membranes.
The contrasting results of the ATP levels in different cohort of patients11,13–15 (this study) indicate that CFS is a complex disease and the current diagnoses may include people with varying molecular dysfunctions. A better categorization of patients with differing cellular defects will allow researchers to better understand the underlying causes and improve treatment efficacy. Future studies are warranted to unravel why and how non-mitochondrial ATP production is activated in some patients, which will yield insights into novel strategies to address the pathological causes.
Enlace al estudio completo: http://www.jnsci.org/files/article/2016/e221.pdf
Intrigadísima a ver qué opina Sergio, es curioso leer lo de la elevada produccion de ATP (aunque se aclare que esta provendría de fuentes no mitocondriales, si es que entiendo bien...
).Este estudio contradice todo lo que hasta ahora sabíamos (Dr. Myhill, disfunción, fallo mitocondrial, menor produccion de ATP, etc)? O no necesariamente?
).
¿Es así?
