Mitofusin-2 (MFN2) (MFN2)

Mitofusin-2 (MFN2) is a dynamin-like GTPase anchored in the outer mitochondrial membrane, where it serves as a master regulator of mitochondrial fusion and network architecture (UniProt P59510) [1]. Beyond its role in fusion, MFN2 is vital for tethering mitochondria to the endoplasmic reticulum, supporting calcium homeostasis, and facilitating axonal transport of mitochondria in neurons (Filadi et al., 2018) [2]. Mutations in the MFN2 gene are the leading cause of Charcot-Marie-Tooth disease type 2A (CMT2A), a debilitating peripheral neuropathy characterized by progressive muscle weakness and sensory loss due to axonal degeneration (PubMed: 31160512) [3]. Therapeutic approaches currently under investigation include adeno-associated virus (AAV)-mediated gene therapy designed to deliver a functional wild-type MFN2 gene to affected neurons (Zhou et al., 2019) [4]. This strategy aims to restore mitochondrial dynamics and metabolic function, potentially halting or reversing the progression of CMT2A. While promising, challenges include achieving precise expression levels to avoid mitochondrial aggregation and managing the immunogenicity associated with viral vectors (Franco et al., 2020) [5].

Other names

Mitofusin-2MFN2CPRP1HSGMARFTransmembrane GTPase MFN2

Gene replacement therapy to restore wild-type protein expression and mitochondrial fusion activity