Figure 3.
Progressive loss of NDUFS3 reveals the modular dynamics of CI disassembly
(A) Scatterplots generated from the liquid chromatography-mass spectrometry (LC-MS) analysis of mitochondrial-enriched fractions corresponding to the duplicate SILAC experiments, comparing untreated 143B−/−NDUFS3 with cells treated with 100 ng/mL Dox for 2, 4, or 8 days. The values of the logarithmic fold change (log2 H/L) for each protein in experiment 1 (exp.1; light untreated, heavy Dox treated) are represented in the x axis. The logarithmic fold-change values (−log2 H/L) derived from experiment 2 (exp.2; heavy untreated, light Dox treated) are represented in the y axis. Each point represents the values for a specific protein. CI subunits and assembly factors are highlighted; CI subunits of the same module are the same color. The group termed “uncertain” includes the subunits with still-unclear domain assignments (Stroud et al., 2016).
(B) Heatmap generated from the mean of the duplicate SILAC experiments for the detected CI subunits at each of the Dox treatment points (2, 4, and 8 days). Grey, not detected either in one or both of the duplicates.
(C) CI subunit relative protein abundance changes induced by repression of NDUFS3 after 2 and 8 days of 100 ng/mL Dox treatment depicted on the structure of the active mouse CI (PDB: 6G2J) (Agip et al., 2018) using ChimeraX version 1.1 (Goddard et al., 2018).
See also Figure S4.