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Evaluating the Role of Mitochondrial Function in Cancer-related Fatigue
Published on: May 17, 2018
Pilot study of peripheral muscle function in primary biliary cirrhosis: potential implications for fatigue
Kieren G Hollingsworth1, Julia L Newton, Roy Taylor
1Newcastle Magnetic Resonance Centre, Newcastle University, Newcastle-upon-Tyne, United Kingdom.
Summary
Primary biliary cirrhosis (PBC) patients show muscle mitochondrial dysfunction and excess acidosis after exercise. This dysfunction is linked to fatigue, impacting recovery time.
Area of Science:
- Hepatology
- Mitochondrial Physiology
- Autoimmune Diseases
Background:
- Primary biliary cirrhosis (PBC) is an autoimmune liver disease often associated with antibodies against the pyruvate dehydrogenase complex (PDC).
- While anti-PDC antibodies inhibit PDC in vitro, in vivo mitochondrial function in PBC remains largely unexamined.
Purpose of the Study:
- To investigate in vivo mitochondrial function and pH regulation in peripheral muscle of PBC patients during exercise.
- To correlate these physiological parameters with clinical fatigue and autoantibody levels.
Main Methods:
- Utilized 31P magnetic resonance spectroscopy to assess mitochondrial function in PBC patients (n=15) and controls (n=20) including chronic fatigue syndrome/myalgic encephalomyelitis and primary sclerosing cholangitis.
- Measurements were taken during incremental exercise (25% and 35% maximal voluntary contraction) to evaluate muscle energetics and pH recovery.
Main Results:
- PBC patients exhibited impaired mitochondrial response to exercise, indicated by a loss of correlation between phosphocreatine (PCr) and adenosine diphosphate (ADP) recovery kinetics.
- Elevated PCr/ADP recovery ratios and excess muscle acidosis were observed in PBC patients, correlating with anti-PDC levels and exercise intensity.
- Prolonged muscle pH recovery time in PBC patients, independent of mitochondrial function, correlated significantly with clinical fatigue.
Conclusions:
- Muscle mitochondrial dysfunction is present in a variable degree in PBC patients, manifesting as exercise-induced acidosis.
- The ability of PBC patients to recover from acidosis is a key determinant of their clinical fatigue levels.
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