Figure 7.

Oxidative respiration is normal in cells expressing MFN2 disease mutants despite mitochondrial clustering. A, Representative oxygen consumption graphs for HEK 293T cells expressing wild-type MFN2 (WT) or disease mutants R94Q or W740S. The arrow indicates the addition of 2,4-dinitrophenol, an uncoupling agent to induce maximal oxidative respiration. The slope of the line indicating the rate of respiration is shown above the curves both before (endogenous respiration) and after (maximal respiration) the addition of the uncoupling agent 2,3-dinitrophenol. B, Fluorescence images of HEK 293T cells expressing wild-type (WT) MFN2 or disease mutant R94Q, together with mito-DsRed2 to visualize mitochondria, showed that these cells form similar mitochondrial aggregates to that seen in primary neurons only in the presence of MFN2 disease mutants. C, Despite the mitochondrial clustering induced by mutant MFN2 proteins, both endogenous and maximal respiration rates were similar in cells expressing wild-type or mutant MFN2 proteins, indicating that mutant MFN2 proteins do not alter mitochondrial oxidative respiration.