MCL-1 Inhibition Results in Mitochondrial Fragmentation in a DRP-1-Dependent Manner
(A–D) (A) Vehicle- and (B) S63845-treated hiPSC-CMs were transfected with mito-tdEos and a small area was photoconverted (see methods). Cells were imaged for 20 min post-conversion to assess mitochondrial network connectivity. Scale: 5 μm. Quantification of the initial converted area normalized to total unconverted area (C) and fold change in converted area after 20 min (D) shows decreased initial connectivity and mitochondrial fusion after treatment with 2 μM S63845 and QVD (MCL-1i).
(E) Quantification of initial converted area normalized to total unconverted area in hiPSC-CMs transfected with control siRNA or siRNA targeting DRP-1 ±MCL-1i (2 μM S63845) and QVD.
(F) Quantification of fold change in converted area after 20 min in same treatments from Figure 4E. Boxplots represent median of three independent experiments and Tukey whiskers.
See also Figure S4.