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. Author manuscript; available in PMC: 2021 Nov 30.
Published in final edited form as: J Med Chem. 2021 Aug 20;64(17):12506–12524. doi: 10.1021/acs.jmedchem.1c00163

Figure 4. Mitochondrial elongation and polarization-enhancing activities of 5 enantiomers.

Figure 4.

A. Dose-response curves for 5A and 5B to increase mitochondrial aspect ratio (length/width) in cultured fibroblasts lacking Mfn1 (left, 5A: EC50 > 10μM, 5B: EC50 = 3.80nM; 95% confidence limits, 2.70-5.28nM) or Mfn2 (right, 5A: EC50 > 10μM, 5B: EC50 = 4.26nM; 95% confidence limits, 2.99-6.04nM). Parallel studies with prototype mitofusin activator 1 are shown for comparison. B. Group data (left) and representative live cell confocal micrographs (right) from Mfn1 and Mfn2 null cells showing mitochondrial elongation (increase in aspect ratio) and reversal of depolarization with 1 μM test compound added for 48 hours. Enlarged mitochondria are shown in insets. Mitochondria staining yellow are highly polarized, i.e. healthy; green staining mitochondria are depolarized and dysfunctional.