MFN1 agonist for mitochondrial dysfunction

Promoting mitochondrial fusion with a small molecule agonist of the outer mitochondrial membrane MFN1 could help restore mitochondrial function in settings of drug toxicity and ischemia/reperfusion injury, and in genetic diseases such as Charcot–Marie–Tooth disease, which is caused by mutations in the related protein MFN2.

A screen of 40 derivatives of the natural compound spiramine identified a candidate that rescued mitochondrial fragmentation and ATP production in MFN2-deficient human and mouse cells in an MFN1-dependent manner, and subsequent biochemical experiments showed the compound bound MFN1 directly and increased its rate of GTP hydrolysis. ...