Abstract
Mutations in mitochondrial DNA (mtDNA) cause disruption of the oxidative phosphorylation chain and impair energy production in cells throughout the human body. Primary mitochondrial disorders due to mtDNA mutations can present with symptoms from adult-onset mono-organ affection to death in infancy due to multi-organ involvement. The heterogeneous phenotypes that patients with a mutation of mtDNA can present with are thought, at least to some extent, to be a result of differences in mtDNA mutation load among patients and even among tissues in the individual. The most common symptom in patients with mitochondrial myopathy (MM) is exercise intolerance. Since mitochondrial function can be assessed directly in skeletal muscle, exercise studies can be used to elucidate the physiological consequences of defective mitochondria due to mtDNA mutations. Moreover, exercise tests have been developed for diagnostic purposes for mitochondrial myopathy. In this review, we present the rationale for exercise testing of patients with MM due to mutations in mtDNA, evaluate the diagnostic yield of exercise tests for MM and touch upon how exercise tests can be used as tools for follow-up to assess disease course or effects of treatment interventions.
Highlights
Primary mitochondrial disease, due to mutations in mitochondrial DNA, is characterized by high variability of clinical presentation
The pronounced involvement of skeletal muscle is thought to be related to the high mitochondrial DNA (mtDNA) mutation load in skeletal muscle [3,7,8] combined with a high oxygen demand that increases up to 100-fold from rest to exercise, which is unmatched by any other tissue [6,9]
Since VO2max is low and correlates directly with mtDNA mutation in skeletal muscle in patients with mitochondrial myopathy (MM) [2,3,7,10], it could be speculated that exercise testing with measurement of VO2max could be a diagnostic tool for patients suspected of MM
Summary
Due to mutations in mitochondrial DNA (mtDNA), is characterized by high variability of clinical presentation. The cardiovascular response to exercise is managed through a similar tight interaction between central and peripheral neural efferent and afferent systems that ensure that cardiac output matches oxygen demand in skeletal muscle. These systems include central command, arterial baroreflex and the exercise pressor reflex/ergoreflex (Figure 3) [42,44,45,46]. With the onset of exercise, the central nervous system generates a sympathoadrenal response that reduces parasympathetic activity to the heart and resets the arterial baroreflex, leading to increased blood and vascular pressure (Figure 3). During the first 30 to 60 s of exercise, anaerobic glycogenolysis and glycolysis is activated maximally allowing
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
