Fuchen Liu1,2, Jianwei Lou1, Dandan Zhao1, Wei Li1, Yuying Zhao1, Xiulian Sun3, Chuanzhu Yan1,4,5. 1. a Department of Neurology , Qilu Hospital of Shandong University , Jinan , China. 2. b Department of Neurobiology, Kavli Institute for Neuroscience , Yale University School of Medicine , New Haven , CT , USA. 3. c Otolaryngology Lab, Qilu Hospital of Shandong University , Jinan , China. 4. d Key Laboratory for Experimental Teratology of the Ministry of Education , School of Medicine, Shandong University , Jinan , China. 5. e Brain Science Research Institute , Shandong University , Jinan , China.
Abstract
PURPOSE: Mitochondrial defects have been associated with a series of muscular diseases. Dysferlinopathy, however, has been rarely reported with mitochondrial dysfunction. Here we report a cohort of dysferlinopathy patients with mitochondrial abnormalities found in muscle. METHODS: Clinical data and muscle pathologies of nine cases with dysferlinopathy were retrospectively studied. mtDNA copy number, protein levels and activities of mitochondrial enzyme complexes were assayed. RESULTS: Nine patients were diagnosed as having dysferlinopathy by DYSF sequencing and quantification of dysferlin levels in muscle homogenates. Muscle biopsies exhibited dystrophic changes (n = 9), ragged-red fibers (n = 9) and cytochrome c oxidase-deficient fibers (n = 9). mtDNA copy number increased significantly in 56% (15/27) of fibers with mitochondrial histology. Protein levels of complex IV subunits II (n = 5), complex III subunit core 2 (n = 2) and complex I NDUFB1 (n = 1) decreased. Impaired activities of complexes I, III and IV were observed in 56%, 33% and 78% of subjects and the activities were reduced by 21%, 18% and 40%, respectively. Besides, loss activities of complexes I/IV and decreased ATP level were also found in fibroblasts from dysferlinopathy. CONCLUSION: Prominent mitochondrial abnormalities are common pathological findings in muscle from dysferlinopathy. Our data indicated that mitochondria may play a significant role in the progression of dysferlinopathy and also highlighted the potential of mitochondrial protective drugs in rescuing the symptoms of dysferlinopathy.
PURPOSE: Mitochondrial defects have been associated with a series of muscular diseases. Dysferlinopathy, however, has been rarely reported with mitochondrial dysfunction. Here we report a cohort of dysferlinopathypatients with mitochondrial abnormalities found in muscle. METHODS: Clinical data and muscle pathologies of nine cases with dysferlinopathy were retrospectively studied. mtDNA copy number, protein levels and activities of mitochondrial enzyme complexes were assayed. RESULTS: Nine patients were diagnosed as having dysferlinopathy by DYSF sequencing and quantification of dysferlin levels in muscle homogenates. Muscle biopsies exhibited dystrophic changes (n = 9), ragged-red fibers (n = 9) and cytochrome c oxidase-deficient fibers (n = 9). mtDNA copy number increased significantly in 56% (15/27) of fibers with mitochondrial histology. Protein levels of complex IV subunits II (n = 5), complex III subunit core 2 (n = 2) and complex I NDUFB1 (n = 1) decreased. Impaired activities of complexes I, III and IV were observed in 56%, 33% and 78% of subjects and the activities were reduced by 21%, 18% and 40%, respectively. Besides, loss activities of complexes I/IV and decreased ATP level were also found in fibroblasts from dysferlinopathy. CONCLUSION: Prominent mitochondrial abnormalities are common pathological findings in muscle from dysferlinopathy. Our data indicated that mitochondria may play a significant role in the progression of dysferlinopathy and also highlighted the potential of mitochondrial protective drugs in rescuing the symptoms of dysferlinopathy.
Authors: Arlek González-Jamett; Walter Vásquez; Gabriela Cifuentes-Riveros; Rafaela Martínez-Pando; Juan C Sáez; Ana M Cárdenas Journal: Biomedicines Date: 2022-02-21
Authors: Amy E Vincent; Hannah S Rosa; Charlotte L Alston; John P Grady; Karolina A Rygiel; Mariana C Rocha; Rita Barresi; Robert W Taylor; Doug M Turnbull Journal: Neuromuscul Disord Date: 2016-08-29 Impact factor: 4.296