Comparison of lymphoblast mitochondria from normal subjects and patients with Barth syndrome using electron microscopic tomography

• Published in: Laboratory investigation Vol. 87; no. 1; pp. 40 - 48
• Main Authors: Acehan, Devrim, Xu, Yang, Stokes, David L, Schlame, Michael
• Format: Journal Article
• Language: English
• Published: New York Elsevier Inc 01.01.2007; Nature Publishing Group US; Nature Publishing; Nature Publishing Group
• Subjects: Acyltransferases; Biological and medical sciences; Biotechnology; cardiomyopathy; Cardiomyopathy, Dilated - genetics; Cardiomyopathy, Dilated - pathology; Cell Line, Transformed - ultrastructure; Child; Child, Preschool; electron microscopic tomography; Fundamental and applied biological sciences. Psychology; Genetic Diseases, X-Linked - pathology; Genetic Diseases, X-Linked - ultrastructure; Humans; Image Processing, Computer-Assisted; Imaging, Three-Dimensional; Infant; Investigative techniques, diagnostic techniques (general aspects); Laboratory Medicine; Lymphocyte Activation; Lymphocytes - ultrastructure; Male; Medical sciences; Medicine; Medicine & Public Health; Microscopy, Electron; Mitochondria - pathology; Mitochondria - ultrastructure; mitochondrial disease; Mitochondrial Diseases - genetics; mitochondrial ultrastructure; Pathology; Proteins - genetics; research-article; skeletal myopathy; Syndrome; Tomography, Optical; Transcription Factors - genetics; mitochondrial ultrastructure; cardiomyopathy; skeletal myopathy; mitochondrial disease; electron microscopic tomography; Biotechnology; Cardiomyopathy; Cardiovascular disease; Hemopathy; Lymphoblast; Enzymopathy; Myocardial disease; Mitochondrial disorder; Osteoarticular system; Barth syndrome; Mitochondria; Ultrastructure; Heart disease; Clinical biology; Tomography; Skeleton; Human; Metabolic diseases; Electron microscopy; Normal; Genetic disease; Striated muscle disease; Bone; Comparative study; Myopathy
• ISSN: 0023-6837; 1530-0307
• DOI: 10.1038/labinvest.3700480

Barth syndrome (BTHS) is a mitochondrial disorder that is caused by mutations in the tafazzin gene, which affects phospholipid composition. To determine whether this defect leads to alterations in the internal three-dimensional organization of mitochondrial membranes, we applied electron microscopic tomography to lymphoblast mitochondria from BTHS patients and controls. Tomograms were formed from 50 and 150 nm sections of chemically fixed lymphoblasts and the data were used to manually segment volumes of relevant structural details. Normal lymphoblast mitochondria contained well-aligned, lamellar cristae with slot-like junctions to the inner boundary membrane. In BTHS, mitochondrial size was more variable and the total mitochondrial volume per cell increased mainly due to clusters of fragmented mitochondria inside nuclear invaginations. However, mitochondria showed reduced cristae density, less cristae alignment, and inhomogeneous cristae distribution. Three-dimensional reconstruction of BTHS mitochondria revealed zones of adhesion of the opposing inner membranes, causing obliteration of the intracrista space. We found small isolated patches of adhesion as well as extended adhesion zones, resulting in sheets of collapsed cristae packaged in multiple concentric layers. We also found large tubular structures (diameter 30–150 nm) that appeared to be derivatives of the adhesion zones. The data suggest that mitochondrial abnormalities of BTHS involve adhesions of inner mitochondrial membranes with subsequent collapse of the intracristae space.