{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T12:35:58Z","timestamp":1791894958479,"version":"4.3.4"},"reference-count":41,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2001,4,27]],"date-time":"2001-04-27T00:00:00Z","timestamp":988329600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Annals of Neurology"],"published-print":{"date-parts":[[2001,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Aerobic training has been shown to increase work and oxidative capacity in patients with mitochondrial myopathies, but the mechanisms underlying improvement are not known. We evaluated physiological (cycle exercise, <jats:sup>31<\/jats:sup>P\u2010MRS), biochemical (enzyme levels), and genetic (proportion of mutant\/wild\u2010type genomes) responses to 14 weeks of bicycle exercise training in 10 patients with heteroplasmic mitochondrial DNA (mtDNA) mutations. Training increased peak work and oxidative capacities (20\u201330%), systemic arteriovenous O<jats:sub>2<\/jats:sub> difference (20%), and <jats:sup>31<\/jats:sup>P\u2010MRS indices of metabolic recovery (35%), consistent with enhanced muscle oxidative phosphorylation. Mitochondrial volume in vastus lateralis biopsies increased significantly (50%) and increases in deficient respiratory chain enzymes were found in patients with Complex I (36%) and Complex IV (25%) defects, whereas decreases occurred in 2 patients with Complex III defects (\u201020%). These results suggest that the cellular basis of improved oxygen utilization is related to training\u2010induced mitochondrial proliferation likely resulting in increased levels of functional, wild\u2010type mtDNA. However, genetic analysis indicated the proportion of wild\u2010type mtDNA was unchanged (3\/9) or fell (6\/9), suggesting a trend toward preferential proliferation of mutant genomes. The long\u2010term implications of training\u2010induced increases in mutant relative to wild\u2010type mtDNA, despite positive physiological and biochemical findings, need to be assessed before aerobic training can be proposed as a general treatment option.<\/jats:p>","DOI":"10.1002\/ana.1050","type":"journal-article","created":{"date-parts":[[2002,9,10]],"date-time":"2002-09-10T23:33:12Z","timestamp":1031700792000},"page":"133-141","source":"Crossref","is-referenced-by-count":192,"title":["Aerobic conditioning in patients with mitochondrial myopathies: Physiological, biochemical, and genetic effects"],"prefix":"10.1002","volume":"50","author":[{"given":"Tanja","family":"Taivassalo","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric A.","family":"Shoubridge","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacqueline","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nancy G.","family":"Kennaway","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Salvatore","family":"DiMauro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Douglas L.","family":"Arnold","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ronald G.","family":"Haller","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2001,7,30]]},"reference":[{"key":"e_1_2_6_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/331717a0"},{"key":"e_1_2_6_3_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.3201231"},{"key":"e_1_2_6_4_2","doi-asserted-by":"publisher","DOI":"10.1002\/bies.950181208"},{"key":"e_1_2_6_5_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.283.5407.1482"},{"key":"e_1_2_6_6_2","first-page":"555","volume-title":"Handbook of physiology: skeletal muscle","author":"Saltin B","year":"1983"},{"key":"e_1_2_6_7_2","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.50.4.1055"},{"key":"e_1_2_6_8_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI114135"},{"key":"e_1_2_6_9_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199909303411404"},{"key":"e_1_2_6_10_2","doi-asserted-by":"publisher","DOI":"10.1002\/1531-8249(199906)45:6<820::AID-ANA22>3.0.CO;2-W"},{"key":"e_1_2_6_11_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng0496-410"},{"key":"e_1_2_6_12_2","unstructured":"AnitoriRP QuanF BuistNRM et al.A novel mutation in the mitochondrial tRNATrp gene in a sporadic case of mitochondrial myopathy. 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