MSGID: 1:317/3 627352fa   
   PID: hpt/lnx 1.9.0-cur 2019-01-08   
   TID: hpt/lnx 1.9.0-cur 2019-01-08   
    Benefits of exercise may vary greatly in primary mitochondrial disease   
    While the benefits of exercise may outweigh the risks, genetic status   
   should be considered when recommending it as therapy    
      
     Date:   
         May 4, 2022   
     Source:   
         Children's Hospital of Philadelphia   
     Summary:   
         Researchers demonstrated that the benefits of endurance exercise   
         can vary based on the type of mutation involved in mitochondrial   
         disease, and while the benefits of exercise tend to outweigh the   
         risks, the mitochondrial genetic status of patients should be   
         taken into consideration when recommending exercise as therapy.   
      
      
      
   FULL STORY   
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   Mitochondria serve as the main source of energy production in our cells,   
   and endurance exercise is generally known to improve the function of   
   mitochondria.   
      
   However, the benefits of exercise in patients with primary mitochondrial   
   diseases, which are heterogeneous and caused by a variety of genetic   
   mutations, were largely unknown.   
      
      
   ==========================================================================   
   In a new study, researchers at Children's Hospital of Philadelphia (CHOP)   
   demonstrated that the benefits of endurance exercise can vary based   
   on the type of mutation involved in mitochondrial disease, and while   
   the benefits of exercise outweigh the risks, the mitochondrial genetic   
   status of patients should be taken into consideration when recommending   
   exercise as therapy. The findings were published online today by the   
   Proceedings of the National Academy of Sciences.   
      
   Primary mitochondrial diseases represent the most prevalent inherited   
   metabolic disorders, affecting approximately 1 in every 4,200   
   people. These disorders can be caused by hundreds of different mutations   
   in the nuclear DNA (DNA within our cells) or mitochondrial DNA (mtDNA, or   
   the DNA within the mitochondria within our cells). 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 like diabetes or   
   neurodegenerative diorders.   
      
   However, these recommendations were based on healthy people without   
   primary mitochondrial disease. Therefore, researchers wanted to determine   
   effectiveness for these patients and whether they are actually benefitting   
   from endurance exercise.   
      
   "There was not a concensus among clinicians who see patients with   
   mitochondrial disease whether endurance exercise truly offers benefits,"   
   said Patrick Schaefer, PhD, a postdoctoral fellow at the Center for   
   Mitochondrial and Epigenomic Medicine at CHOP and first author of the   
   study. "Exercise helps create more mitochondria, but if those mitochondria   
   still have the mutations associated with primary mitochondrial disease,   
   there is a chance that exercise may put some patients at risk."  Because   
   of the heterogeneity of primary mitochondrial disease among patients, the   
   researchers used animal models to study five mutations responsible for the   
   disease. The goal of the study was to determine the relationship between   
   mitochondrial mutations, endurance exercise response, and the underlying   
   molecular pathways in these models with distinct mitochondrial mutations.   
      
   The study found that endurance exercise had different impacts on the   
   models depending on the mutation involved. Exercise improved response   
   in the model with the mtDNA ND6 mutation in complex I. The model with   
   a CO1 mutation affecting complex IV showed significantly fewer positive   
   effects related to exercise, and the model with a ND5 complex 1 mutation   
   did not respond to exercise at all. In the model that was deficient in   
   nuclear DNA Ant1, endurance exercise actually worsened cardiomyopathy.   
      
   Additionally, the researchers were able to correlate the gene expression   
   profile of skeletal muscle and heart in the model with exercise response   
   and identified oxidative phosphorylation, amino acid metabolism, and   
   cell cycle regulation as key pathways in exercise response, suggesting   
   how the model might be adapted to study exercise responses in humans   
   with primary mitochondrial disease.   
      
   Despite mixed responses of the models used in this study, the authors note   
   that the benefits of exercise outweigh the risks in most cases. However,   
   the physical and mitochondrial status of the patient should be taken into   
   account when recommending therapeutic exercises. Additionally, the study   
   could help researchers identify biomarkers and pathways to help predict   
   the mitochondrial response to exercise both in mitochondrial patients   
   and the healthy population harboring different mitochondrial haplogroups.   
      
   "This work is of fundamental importance in demonstrating that individuals   
   with different mitochondrial bioenergetics will respond differently   
   to endurance exercise," said senior study author Douglas C. Wallace,   
   PhD, director of the Center for Mitochondrial and Epigenomic Medicine   
   at CHOP and the Michael and Charles Barnett Endowed Chair in Pediatric   
   Mitochondrial Medicine and Metabolic Diseases. "This is of broad relevance   
   to individuals ranging from athletes to patients with mitochondrial   
   disease, and everyone in between."  This study was supported by the German   
   Research Foundation through grant SCHA 2182/1-1, the National Institutes   
   of Health grants NS021328, MH108592, and OD010944, and U.S. Department   
   of Defense grants W81XWH16-1-0401 and W81XWH-21- 1-0128. Schematics were   
   created with BioRender.com.   
      
      
   ==========================================================================   
   Story Source: Materials provided by   
   Children's_Hospital_of_Philadelphia. Note: Content may be edited for   
   style and length.   
      
      
   ==========================================================================   
   Journal Reference:   
      1. Patrick M. Schaefer, Komal Rathi, Arrienne Butic, Wendy Tan,   
      Katherine   
         Mitchell, Douglas C. Wallace. Mitochondrial mutations alter   
         endurance exercise response and determinants in mice. Proceedings   
         of the National Academy of Sciences, 2022; 119 (18) DOI:   
         10.1073/pnas.2200549119   
   ==========================================================================   
      
   Link to news story:   
   https://www.sciencedaily.com/releases/2022/05/220504110430.htm   
      
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