Chen et al. find that evening out mitochondrial fusion and fission allows the organelles to regain their normal function.

Mutations in genes that control mitochondrial fusion or fission are responsible for various diseases, including dominant optic atrophy. In all of these diseases, either fusion or fission is defective, and one potential therapeutic approach is to restore the balance between the two opposing processes.

To test whether this approach is feasible, Chen et al. engineered mice to lack Mff, a gene that spurs mitochondrial fission. Although the mice had defects in many of their organs, the most severe abnormalities were in the heart. The animals developed dilated cardiomyopathy, in which the heart enlarges and its walls thin. The condition typically killed the rodents when they were around 13 weeks old. Loss of Mff also caused metabolic defects in the animals. ATP levels fell by 50%, and the main respiratory complexes were sluggish.

The researchers then asked if reducing mitochondrial fusion could correct these problems. They found that mice that are deficient in Mff and the fusion-promoting gene Mfn1 had normal hearts and lifespans. In fact, the rodents’ mitochondria were more efficient than those of healthy mice, sustaining a higher level of oxygen consumption. The animals missing both genes weren’t normal, however. The male animals were sterile because of a defect in the testes.

Although fusion and fission were reduced in the animals lacking Mff and Mfn1, the two processes were in equilibrium, enabling mitochondria to work normally. Thus drugs that restore the balance between fusion and fission could be beneficial for diseases such as dominant optic atrophy.

, et al
J. Cell Biol.

Author notes

Text by Mitch Leslie