Myoferlin targeting triggers mitophagy and primes ferroptosis in pancreatic cancer cells.

ABSTRACT: Myoferlin, an emerging oncoprotein, has been associated with a low survival in several cancer types including pancreas ductal adenocarcinoma where it controls mitochondria structure and respiratory functions. Owing to the high susceptibility of KRAS-mutated cancer cells to iron-dependent cell death, ferroptosis, and to the high iron content in mitochondria, we investigated the relation existing between mitochondrial integrity and iron-dependent cell death. We discovered that myoferlin targeting with WJ460 pharmacological compound triggered mitophagy and ROS accumulation culminating with lipid peroxidation and apoptosis-independent cell death. WJ460 caused a reduction of the abundance of ferroptosis core regulators x_c^- cystine/glutamate transporter and GPX-4. Mitophagy

SUBMITTER: Rademaker G 

PROVIDER: S-EPMC9096673 | biostudies-literature | 2022 Jul

REPOSITORIES: biostudies-literature