Figure 6.

Abnormal Mitochondrial Ultrastructure in CODAS Cells

(A–D) Transmission electron micrographs were generated from cell lines of (A and C) two CODAS-syndrome-affected children homozygous for p.Arg721Gly (Gly⁷²¹/Gly⁷²¹) and (B and D, respectively) their heterozygous unaffected mothers (Arg⁷²¹/Gly⁷²¹). (A and C) In CODAS cells, 43% of mitochondria (n = 59 cells, p < 0.001) display abnormal morphology, including swollen intracristal space and/or vesiculated cristae and electron-dense aggregations (white arrows). The mitochondrion below the asterisk in (A′) appears to be in transition toward the vesiculated state when it is compared to the normal mitochondrion to the left of the asterisk. (B and D) The mothers’ cells display normal mitochondrial morphology (e.g., arrowheads); 14% show swelling of the intracristal space (n = 63 cells, p < 0.001) (N = nucleus). Scale bars represent 1 μm in (A–D) and 0.3 μm in magnified regions (A′–D′). The fathers’ cells show normal mitochondrial morphology, and only 5.2% show cristal-space swelling (n = 48) (Figure S6).