Figure 5.

Quantitative Proteomic Analysis of Fibroblasts from an Affected Subject with MRPS34 Mutations Identifies a General Decrease in Small Mitoribosomal and OXPHOS Subunit Proteins

(A) Quantitative mass spectrometry of mitochondrial proteins in fibroblasts from subject 1 and control individuals demonstrates downregulation of small mitoribosome subunits (red dots), as well as OXPHOS subunits (blue dots), in subject 1. In contrast, the levels of large mitoribosome subunits (yellow dots) in subject 1 are generally unaffected. Proteins examined in this study by SDS-PAGE and observed to have reduced levels are indicated by the text labels. The horizontal line within the volcano plot represents a significance value of p = 0.05, where the levels of proteins represented above the horizontal p = 0.05 line was regarded as significantly different from control individuals. The two dashed vertical lines indicate Log2 changes of >0.5 up- or downregulation relative to control individuals.

(B) OXPHOS and mitoribosome protein levels in subject 1 represented as a ratio of the control mean. Hashes denote groups that were significantly reduced in subject 1 relative to control individuals (all with p value < 0.0001). The middle bar represents the mean value, while the upper and lower bars represent the 95% confidence interval of the mean value. Each dot represents a single protein.

(C) Changes in mitoribosome protein levels between subject 1 relative to control individuals mapped to the structure of the human mitoribosome. As per the inset scale, proteins colored in blue are decreased, and those colored in red are increased, in subject 1 relative to control individuals. Grey indicates no data; yellow indicates MRPS34.

(D) Changes in OXPHOS subunit levels for complexes I–IV mapped to homologous subunits of the relevant structure. Color scale as per (C).