Metastatic breast cancer cells are selectively dependent on the mitochondrial cristae-shaping protein OPA1.

ABSTRACT: In breast cancer, the inner mitochondrial membrane fusion protein Optic Atrophy 1 (OPA1) is upregulated and its inhibition reverses acquired chemoresistance. However, it remains unclear whether OPA1 inhibition also targets normal breast cells. We show that OPA1 upregulation is a hallmark of metastatic breast cancer cells, which are selectively susceptible to OPA1 inhibition compared to isogenic normal or localized tumor cells. In an isogenic model spanning normal, transformed, and metastatic breast cancer cells, levels of Mitofusin 1 (MFN1) progressively declined while dynamin related protein 1 (DRP1) became increasingly active, correlating with fragmented mitochondria during cancer progression. Meanwhile, OPA1 levels were elevated in invasive cells characterized by mitochondrial fragmenta

SUBMITTER: Diokmetzidou A 

PROVIDER: S-EPMC12279937 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature