Fig. 7: PSMC5 variants impair mitochondrial homeostasis, ribosome biogenesis and lipid metabolism in T cells.

a Volcano plot of differentially expressed proteins in T cells from five individuals (four samples: three separate samples for S14, S15, S25, plus pooled sample from S36 and S37) versus nine controls, identified by mass spectrometry (n = 13 samples; p ≤ 0.05; log₂FC ≥ 1 or ≤–1; Student’s t-test). Red and blue dots indicate enriched or depleted pathways; green dots highlight mitochondrial proteins (MitoCarta 3.0)⁶⁹. b Proteomics: Network clustering and pathway analysis of dysregulated proteins (p ≤ 0.05; –2 ≤ FC ≤ 2; Student’s t-test) using GO, KEGG, and STRING databases in Cytoscape (STRING Homo sapiens background). c Untargeted lipidomics of T cells from patients (S1, S7, S14, S15, S23, S25, S37; n = 7) and matched controls (parents and/or siblings; n = 6) revealed distinct lipid profiles by PCA in positive and negative ion modes (patients: blue; controls: red). d Fold-change analysis of lipid classes showed significant alterations in patient T cells (*p < 0.05, **p < 0.01, ***p < 0.001; two-tailed Student’s t-test). e Mitophagy was assessed by flow cytometry in T cells from patients (S1, S7, S14, S15, S25, S36, S37) and healthy donors (related and unrelated) using Mtphagy dye (100 nM, overnight; B4 channel, PE-Vio 770). Percentages of mitophagy-positive cells were significantly increased in patients (**p = 0.002, two-tailed Mann-Whitney U test). Data are presented as the mean percentage of mitophagy-positive cells ±SEM of biological replicates for controls (90.09 ± 3.330, n = 7) and patients (70.29 ± 3.525, n = 7).