MARCHF5

MARCHF5 encodes Membrane-Associated Ring-CH-Type Finger 5 (MARCH5), also known as MITOL. As a mitochondrial-localized E3 ubiquitin ligase, it regulates mitochondrial dynamics by ubiquitinating key substrates like DRP1 (a fission protein) and Mfn1/2 (fusion proteins), balancing fusion and fission. It also participates in mitochondrial quality control and autophagy pathways to maintain cellular homeostasis.
Dysregulation of MARCH5 links to neurodegenerative disorders (e.g., Parkinson’s disease, where impaired mitochondrial function drives neuronal loss) and cancers (e.g., hepatocellular carcinoma, tied to altered mitochondrial dynamics). Drug development targeting MARCH5 is preclinical, with efforts to identify small molecules modulating its ligase activity for therapeutic use.