Inhibiting MARCH5/Mfn2 signaling as an alternative strategy to protect cardiomyocytes from hypoxia-induced mitochondrial dysfunction.

ABSTRACT: The mitochondrial E3 ubiquitin ligase membrane-associated RING-CH-type finger 5 (MARCH5) and the GTPase Mitofusin 2 (Mfn2) both play crucial roles in regulating mitochondrial dynamics, which are essential for cellular homeostasis. Dysregulation of the MARCH5/Mfn2 signaling has been implicated in mitochondrial dysfunction, a key factor in cardiovascular diseases (CVDs). To investigate the therapeutic potential of targeting this interaction, we developed a novel peptide, CVP-220, designed to specifically disrupt the MARCH5/Mfn2 protein interaction. Using a hypoxia-reoxygenation (H/R) injury model in rat cardiomyocyte cell lines, CVP-220 demonstrated significant cardioprotective effects. Treatment with CVP-220 enhanced cell viability by 30 % compared to untreated controls and reduced reactive

SUBMITTER: Zoabi FH 

PROVIDER: S-EPMC12275895 | biostudies-literature | 2025

REPOSITORIES: biostudies-literature