overview: The benefits of endurance exercise may vary depending on the type of mutation associated with primary mitochondrial disease, new studies report.
Source: chop
Mitochondria function as the main source of energy for our cells, and endurance exercise is generally known to improve mitochondrial function. However, little is known about the benefits of exercise in patients with primary mitochondrial disease that are heterogeneous and caused by various genetic mutations.
In a new study, researchers at the Children’s Hospital of Philadelphia (CHOP) found that the benefits of endurance exercise can vary based on the type of mutation involved in mitochondrial disease, although the benefits of exercise outweigh the risks. The patient’s mitochondrial genetic status has been shown and should be taken into account when recommending exercise as a treatment.
Survey results published online today Minutes of the National Academy of Sciences..
Primary mitochondrial disease is the most common inborn error of metabolism, affecting about 1 in 4,200 people. These disorders can be caused by hundreds of different mutations in nuclear DNA (intracellular DNA) or mitochondrial DNA (mtDNA, or intracellular mitochondrial DNA).
Universal treatments for these patients are limited. However, endurance exercise has been shown to improve mitochondrial function in healthy people and reduce the risk of developing secondary metabolic disorders such as diabetes and neurodegenerative diseases.
However, these recommendations are based on healthy people without primary mitochondrial disease. Therefore, researchers wanted to determine the effectiveness of these patients and whether they actually benefited from endurance exercise.
“There was no consensus among clinicians looking at patients with mitochondrial disease whether endurance exercise really benefits,” said CHOP, a postdoctoral fellow at the Center for Mitochondrial and Epigenomic Medicine and lead author of the study. Dr. Patrick Schaefer said. ..
“Exercise helps to produce more mitochondria, but if those mitochondria still have mutations associated with primary mitochondrial disease, exercise can put some patients at risk. “
Due to the heterogeneity of primary mitochondrial disease among patients, researchers used animal models to study the five disease-causing mutations.
The purpose of this study was to determine the relationship between mitochondrial mutations, endurance motor responses, and the underlying molecular pathways of these models with distinct mitochondrial mutations.
This study found that endurance exercise affects the model differently depending on the mutations involved. Exercise an improved response in a model with the mtDNAND6 mutation in complex I.
Models with CO1 mutations affecting Complex IV had significantly less positive effects associated with exercise, and models with ND5 Complex 1 mutation did not respond to exercise at all. In models lacking nuclear DNA Ant1, endurance exercise actually exacerbated cardiomyopathy.
In addition, researchers can correlate the model’s skeletal muscle and heart gene expression profiles with motor response, identifying oxidative phosphorylation, amino acid metabolism, and cell cycle regulation as key pathways for motor response, and the model To study the human motor response to primary mitochondrial disease, which suggested how it is adapted.
The model used in this study responded mixedly, but the authors state that in most cases the benefits of exercise outweigh the risks. However, when recommending therapeutic exercise, the patient’s physical and mitochondrial conditions should be taken into account.
In addition, this study may help researchers identify biomarkers and pathways that help predict mitochondrial responses that exercise in both mitochondrial patients and healthy populations with different mitochondrial haplogroups.
“This study is fundamentally important in demonstrating that individuals with different mitochondrial bioenergies respond differently to endurance exercise,” said a senior study, director of CHOP’s Center for Mitochondrial and Epigenome Medicine. The author, Dr. Douglas C. Wallace, said. Michael and Charles Burnett conferred chairs on pediatric mitochondrial medicine and metabolic disorders.
“This is widely relevant to individuals, from athletes to patients with mitochondrial disease, and everyone in between.”
About this genetics and motor research news
author: Press office
Source: chop
contact: Press Office – CHOP
image: The image is in the public domain
Independent research: Closed access.
Patrick M. Schaefer et al. “Mitochondrial mutations alter the endurance motor response and determinants of mice.” PNAS
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Mitochondrial mutations alter the endurance motor response and determinants of mice
Primary mitochondrial disease (PMD) is a heterogeneous group of metabolic disorders that can be caused by hundreds of mutations in both mitochondrial DNA (mtDNA) and nuclear DNA (nDNA) genes. Current treatment approaches are limited, but one approach is exercise training.
Endurance exercise is known to improve mitochondrial function in healthy subjects and reduce the risk of secondary metabolic disorders such as diabetes and neurodegenerative diseases. However, in PMD, the benefits of endurance exercise are not clear, and while exercise may be beneficial for some mitochondrial disorders, it is contraindicated for other mitochondrial disorders.
Here, we investigate the effect of endurance exercise regimen on a mouse model of PMD with distinct mitochondrial mutations.
The mtDNA ND6 mutation in complex I showed improvement in response to exercise, but mice with the CO1 mutation affecting complex IV showed significantly less positive effects, and mice with the ND5 complex I mutation showed exercise. Indicates that it did not respond to. In mice lacking the nDNA adenine nucleotide translocase 1 (Ant1), endurance exercise actually exacerbated dilated cardiomyopathy.
Correlates gene expression profiles of skeletal muscle and heart with oxidative phosphorylation, amino acid metabolism, and physiological motor responses in which matrix (extracellular matrix) has been identified. [ECM]) Cell cycle regulation as an important pathway for structure and motor response. This underscores the important role of mitochondria in determining athletic performance and response.
As a result, the benefits of endurance exercise in PMD are strongly dependent on the underlying mutation, but our results suggest a general beneficial effect.
