Mfn2-mediated mitochondrial fusion alleviates doxorubicin-induced cardiotoxicity with enhancing its anticancer activity through metabolic switch.

ABSTRACT: Imbalanced mitochondrial dynamics including inhibited mitochondrial fusion is associated with cardiac dysfunction as well as tumorigenesis. This study sought to explore the effects of promoting mitochondrial fusion on doxorubicin(Dox)-induced cardiotoxicity and its antitumor efficacy, with a focus on the underlying metabolic mechanisms. Herein, the inhibition of Mfn2-mediated mitochondrial fusion was identified as a key phenotype in Dox-induced cardiotoxicity. Restoration of Mfn2-mediated mitochondrial fusion enhanced mitochondrial oxidative metabolism, reduced cellular injury/apoptosis and inhibited mitochondria-derived oxidative stress in the Dox-treated cardiomyocytes. Application of lentivirus expressing Drp1 (mitochondrial fusion inhibitor) or Rote/Anti A (mitochondrial complex I/III

SUBMITTER: Ding M 

PROVIDER: S-EPMC9006862 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature