Neurotrophin-4 is up-regulated in ragged-red fibers associated with pathogenic mitochondrial DNA mutations.
Ragged-red fibers (RRFs) are found more frequently in highly oxidative type I fibers than in glycolytic type II fibers in the muscle of many patients with mitochondrial myopathies. Neurotrophin-4 (NT-4), a neuronal signaling molecule, is also expressed in skeletal muscle, predominantly in type I fibers. We found that NT-4 protein and mRNA were present in both type I and type II fibers but were up-regulated in RRFs of patients with mitochondrial encephalomyopathies; it is noteworthy that NT-4 was not up-regulated in muscle fibers from healthy aerobically trained athletes. Thus, NT-4 might represent a member of a new class of candidate molecules involved in the compensatory adjustments of muscle fibers to oxidative dysfunction, and may even play a role as a signaling molecule for mitochondrial proliferation.
Walker
U A
UA
Department of Neurology, Columbia University College of Physicians and Surgeons, New York, NY 10032, USA.
Schon
E A
EA
D001706:Biopsy; D004272:DNA, Mitochondrial / Q000235:genetics*; D005786:Gene Expression Regulation; D006801:Humans; D008931:Mitochondria, Muscle / Q000378:metabolism / Q000473:pathology; D017240:Mitochondrial Myopathies / Q000378:metabolism* / Q000473:pathology; D018485:Muscle Fibers, Skeletal / Q000378:metabolism / Q000473:pathology; D018482:Muscle, Skeletal / Q000378:metabolism* / Q000473:pathology; D009154:Mutation; D009414:Nerve Growth Factors / Q000032:analysis / Q000096:biosynthesis*; D012333:RNA, Messenger / Q000096:biosynthesis; D013177:Sports; D013385:Succinate Dehydrogenase / Q000032:analysis; D014158:Transcription, Genetic
D004272:DNA, Mitochondrial; D009414:Nerve Growth Factors; D012333:RNA, Messenger; D013385:Succinate Dehydrogenase; C073922:neurotrophin 4