E3 ubiquitin-protein ligase MARCHF5 (MARCHF5)

E3 ubiquitin-protein ligase MARCHF5 is an enzyme of the mitochondrial outer membrane that facilitates the transfer of ubiquitin to substrate proteins, thereby regulating their degradation and turnover[1][2][3][4]. MARCHF5 is essential in controlling mitochondrial dynamics by ubiquitinating proteins such as Drp1, mitofusin 1, and mitofusin 2, which mediate mitochondrial fission and fusion. Through these actions, MARCHF5 maintains mitochondrial morphology, supports cell survival, and prevents inappropriate apoptosis and cellular senescence. MARCHF5 also regulates immune response pathways by targeting adaptor proteins involved in antiviral signaling for degradation[4]. Dysregulation of MARCHF5 has been implicated in cancer, especially in certain virus-related lymphomas where it cooperates with anti-apoptotic factors to promote tumor cell survival, as well as in the maintenance of mitochondrial integrity in neurodegeneration. As of 2025, there are no approved drugs that directly target MARCHF5, but its central role in apoptosis and mitochondrial function makes it a potential candidate for therapeutic intervention in cancer and other diseases involving dysregulated cell death[2][3][4].

Other names

Membrane-associated RING-CH-type finger 5MARCH5RNF153MARCH-VMITOLMembrane-associated RING finger protein 5Membrane-associated RING-CH protein VMitochondrial ubiquitin ligaseRING finger protein 153RING-type E3 ubiquitin transferase MARCHF5FLJ20445

For hypothetical or future drugs: inhibition of MARCHF5 could impair mitochondrial protein ubiquitination and modify cell survival/apoptosis pathways (potential cancer therapy target). Modulation of MARCHF5 function might alter degradation of apoptotic or mitochondrial dynamics regulators.