Membrane Associated Ring Finger Protein 5 (MARCH5)

MARCH5 is a ubiquitin ligase of the mitochondrial outer membrane that plays a role in the control of mitochondrial morphology by regulating mitofusin-2 (MFN2) and DRP1 (DNM1L).

Immunofluorescence studies showed that overexpression of MARCH5 in COS-7 cells promoted formation of aberrant, elongated mitochondria, and mitochondrial elongation could be prevented by coexpression of an MFN2 mutant lacking transmembrane domains. Expression of MARCH5 with mutations in the RING finger resulted in mitochondrial fragmentation and accumulation of punctate mitochondria in the perinuclear region. Immunoprecipitation analysis of transfected HeLa cells showed that MARCH5 bound endogenous MFN2 and DRP1, including ubiquitinated DRP1 species.