title: The Spectrum of Mitochondrial Ultrastructural Defects in Mitochondrial Myopathy.
abstract: Mitochondrial functions are intrinsically linked to their morphology and membrane ultrastructure. Characterizing abnormal mitochondrial structural features may thus provide insight into the underlying pathogenesis of inherited and acquired mitochondrial diseases. Following a systematic literature review on ultrastructural defects in mitochondrial myopathy, we investigated skeletal muscle biopsies from seven subjects with genetically defined mtDNA mutations. Mitochondrial ultrastructure and morphology were characterized using two complimentary approaches: transmission electron microscopy (TEM) and serial block face scanning EM (SBF-SEM) with 3D reconstruction. Six ultrastructural abnormalities were identified including i) paracrystalline inclusions, ii) linearization of cristae and abnormal angular features, iii) concentric layering of cristae membranes, iv) matrix compartmentalization, v) nanotunelling, and vi) donut-shaped mitochondria. In light of recent molecular advances in mitochondrial biology, these findings reveal novel aspects of mitochondrial ultrastructure and morphology in human tissues with implications for understanding the mechanisms linking mitochondrial dysfunction to disease.
authors: Wellcome Trust Centre for Mitochondrial Research, Institute of Neurosciences, Newcastle University, Newcastle upon Tyne, UK.
authors: Amy E
authors: AE
authors: Vincent
authors: Wellcome Trust Centre for Mitochondrial Research, Institute of Neurosciences, Newcastle University, Newcastle upon Tyne, UK.
authors: Yi Shiau
authors: YS
authors: Ng
authors: EM Research Services, Newcastle University, Newcastle upon Tyne, UK.
authors: Kathryn
authors: K
authors: White
authors: EM Research Services, Newcastle University, Newcastle upon Tyne, UK.
authors: Tracey
authors: T
authors: Davey
authors: Wadsworth Center, New York State Department of Health, Albany, NY, USA.
authors: Carmen
authors: C
authors: Mannella
authors: Wellcome Trust Centre for Mitochondrial Research, Institute of Neurosciences, Newcastle University, Newcastle upon Tyne, UK.
authors: Gavin
authors: G
authors: Falkous
authors: Wellcome Trust Centre for Mitochondrial Research, Institute of Neurosciences, Newcastle University, Newcastle upon Tyne, UK.
authors: Catherine
authors: C
authors: Feeney
authors: Wellcome Trust Centre for Mitochondrial Research, Institute of Neurosciences, Newcastle University, Newcastle upon Tyne, UK.
authors: Andrew M
authors: AM
authors: Schaefer
authors: Wellcome Trust Centre for Mitochondrial Research, Institute of Neurosciences, Newcastle University, Newcastle upon Tyne, UK.
authors: Robert
authors: R
authors: McFarland
authors: Wellcome Trust Centre for Mitochondrial Research, Institute of Neurosciences, Newcastle University, Newcastle upon Tyne, UK.
authors: Grainne S
authors: GS
authors: Gorman
authors: Wellcome Trust Centre for Mitochondrial Research, Institute of Neurosciences, Newcastle University, Newcastle upon Tyne, UK.
authors: Robert W
authors: RW
authors: Taylor
authors: Wellcome Trust Centre for Mitochondrial Research, Institute of Neurosciences, Newcastle University, Newcastle upon Tyne, UK.
authors: Doug M
authors: DM
authors: Turnbull
authors: Department of Psychiatry, Division of Behavioral Medicine, Columbia University Medical Center, New York, NY, USA.|Department of Neurology and Columbia Translational Neuroscience Initiative, H. Houston Merritt Center, Columbia University Medical Center, New York, NY, USA.
authors: Martin
authors: M
authors: Picard
mesh_terms: D000368:Aged; D001706:Biopsy; D004272:DNA, Mitochondrial / Q000235:genetics; D005260:Female; D006801:Humans; D008855:Microscopy, Electron, Scanning / Q000379:methods*; D046529:Microscopy, Electron, Transmission / Q000379:methods*; D008875:Middle Aged; D008931:Mitochondria, Muscle / Q000473:pathology / Q000648:ultrastructure*; D017240:Mitochondrial Myopathies / Q000000981:diagnostic imaging / Q000235:genetics / Q000473:pathology*; D018482:Muscle, Skeletal / Q000166:cytology* / Q000000981:diagnostic imaging / Q000473:pathology; D009154:Mutation; D055815:Young Adult
chemical_list: D004272:DNA, Mitochondrial