Mitochondria fusion and division can produce the majority of energy to sustain cellular activity.
Mitochondria is a highly dynamic organelle. It can undergo the physiological process of fusion and fission. In different cell types, the morphology varies among small spheres, short rods, or long tubules. This dynamism allows mitochondria to exchange components (e.g. lipid membranes, proteins). Additionally, it promotes the repair and removal of defective mitochondria.
The fusion of mitochondrial contains two steps, the first step requires the fusion of the outer mitochondrial membrane (OMM). Besides the second step requires the fusion of the inner mitochondrial membrane and is mediated by optic atrophy-1 (OPA1). It is reported that loss of either MFN1/2 or OPA1 proteins may result in hyper-fragmented mitochondria. Defective MFN2 mutants may lead to the development of diseases, such as Charcot-Marie-Tooth disease type 2A (CMT2A) and metabolic disorders.
In this article, we will introduce a mitofusin activator MASM7.
MASM7 is able to regulate directly positively MFN1/2 activity and subsequently mitochondrial fusion. MASM7 increases Mito AR with an EC50 value of 75 nM in MEFs cells. The result also shows that MASM7 direct binds to the HR2 domain of MFN2 thereby localized at mitochondria. The Kd value of direct binding to the HR2 domain of MFN2 is 1.1 μM. MASM7 does not induce DNA damage and has no effects on cellular viability over the course of 72 h.
This compound MASM7 promotes the pro-tethering conformation of MFN1/2 to enable mitochondrial fusion. researchers also find that MASM7 increases the GTP-dependent MFN2 higher-order oligomers. As a result, it modulates the levels of pro-fusion oligomers and upregulates the extent of fusion among mitochondria.
In conclusion, the discovery of MASM7 has the potential for research disorders where impaired mitochondrial dynamics contribute to pathogenesis.