Extended Data Fig. 3: YME1L reshapes the mitochondrial proteome independently of OMA1.
From: Lipid signalling drives proteolytic rewiring of mitochondria by YME1L
a, Box plot analysis of the log2 ratio distribution comparing hypoxia and normoxia in WT and Yme1l−/− MEFs of total proteins and mitochondrial proteins. P values calculated by Wilcoxon sum-rank test. Centre lines denote medians, box limits denote 25th and 75th percentiles; whiskers denote maxima and minima (1.5 times the interquartile range). Data located outside the maxima or minima were denoted as outliers and removed. b, Volcano plot representation of proteins determined by quantitative mass spectrometry after isolation of mitochondria from WT and Yme1l−/− MEFs cultivated under normoxic conditions (dataset as in Fig. 1g, n = 5 independent experiments, two-tailed t-test). Filled plots indicate proteins that differ significantly between Yme1l−/− and WT MEFs at a permutation-based estimated FDR < 0.05. Among these, mitochondrial proteins (according to Gene Ontology Cellular Component) are highlighted in blue. Mitochondrial proteins enriched in Yme1l−/− compared to WT are putative YME1L substrates (class I or II). c, d, Volcano plots of mitochondrial protein changes in hypoxia versus normoxia from WT (c) or Yme1l−/− (d) MEFs (dataset as in Fig. 1g, n = 5 independent experiments, two-tailed t-test). Class I YME1L substrates are highlighted in red. e, Z-score of log2-transformed LFQ intensities of class I YME1L substrates in WT, Oma1−/− and Oma1−/−Yme1l−/− MEFs treated as in Fig. 1g (n = 5 independent experiments). f, SDS–PAGE and immunoblot analysis of WT, Yme1l−/− and Oma1−/− MEFs cultured in normoxia (21% O2) or hypoxia (0.5% O2) for 24 h. # denotes nonspecific cross-reaction (n = 1 experiment). g, Spheroid surface area of the indicated HEK293 cell lines after 7 days (means from 16 spheroids shown, n = 1 experiment).
