Extended Data Fig. 2: Integration of seven mitophagy screens.
From: The ADP/ATP translocase drives mitophagy independent of nucleotide exchange
a, GSEA of mitophagy accelerators. The top 1% of genes in aggregate Z-score were analysed using ToppGene Suite31,43. Representative functional categories and Bonferroni-corrected P values are shown. b, Proportion of genes encoding mitochondrial proteins annotated in MitoCarta2.044 in the top 1% of mitophagy accelerators and decelerators (left), and percentage of MitoCarta2.0 member genes identified as being either accelerators (green) or decelerators (red) of mitophagy (right). c, Five functional classes of proteins, based on MitoCarta2.0 annotations, were present in the top 1% of mitophagy accelerators. The representation of each class within the top 1% was compared to its representation in MitoCarta2.0 via a two-tailed Fisher’s exact test. d, Box-and-whisker plots of most significant mitophagy accelerator hits in each of the seven screens. Line, median; box, 75th–25th percentiles; whiskers (blue dots), 99th–1st percentiles. Genes involved in oxidative phosphorylation (OXPHOS) are indicated in yellow. Pathway enrichment was calculated using a Kolmogorov–Smirnov test. e, GSEA enrichment plot for OXPHOS (top) and ranked aggregate Z-scores of all genes (bottom). OXPHOS genes are indicated in yellow. f, GSEA of mitophagy decelerators analysed as in a. g–i, Genes in the KEGG endosomal sorting complexes required for transport (ESCRT) (g), homotypic fusion and vacuole protein sorting (HOPS) (h), and autophagosome (i) pathways. Genes identified as mitophagy accelerators or decelerators are indicated in green and red, respectively. The diameter of each circle is proportional to the Z-score of the indicated gene. j, Principal component (PC) analysis biplot summarizing variation across the seven screens based on cumulative Z-scores of the top 100 genes, displayed as arrows. Autophagy-related genes are indicated. k, Mitochondrial membrane potential assessed by flow cytometry for TMRE is disrupted in CCCP treatment, but is increased after treatment with OAR cocktail. Similar results were obtained in two biological replicates.
