Targeting the MARCH5-MFN2 axis to enhance mitochondrial fusion and sensitize multiple myeloma cells to venetoclax.

ABSTRACT:

Background

Accumulating evidence suggests that mitochondrial fission and fusion events are imbalanced in cancer due to defective activity of their key regulators. In this study, we investigated the functional role of the E3 ubiquitin ligase Membrane-Associated Ring-CH-Type Finger 5 (MARCH5) in regulating cell growth, metabolic reprogramming and drug resistance in multiple myeloma (MM) through the negative regulation of the mitochondrial fusion driver mitofusin 2 (MFN2).

Methods

Cell viability and apoptosis were evaluated in MM cell lines or in co-culture with stromal cells using the CellTiter-Glo® Cell Viability Assay and Annexin V/7-AAD staining, respectively. Clonogenic potential was assessed using methylcellulose-based colony formation assays. Protein stability was determ

SUBMITTER: Valentino I 

PROVIDER: S-EPMC12355794 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature