Targeting mitochondrial proteases CLPP and LONP1 via disruption of mitochondrial redox homeostasis induces proteotoxic stress and suppresses tumor progression.

ABSTRACT:

Background

Cancer cells, which rely heavily on mitochondria for their energy demands and oncometabolites, have a high mitochondrial load, often associated with an aggressive, invasive, and metastatic phenotype. Mitochondrial ROS (mtROS), which play a causal role in cancer, represent the Achilles' heel of cancer since excessive mtROS causes protein misfolding/aggregation, resulting in cell death via proteotoxic stress. Furthermore, the detailed underlying mechanism(s) of mitochondrial oxidative stress-induced cell death remain obscure.

Methods

Cell growth was estimated by MTT assay, clonogenic assay, live-cell imaging and flow cytometry. Intracellular ROS, mtROS, glutathione and antioxidant levels were studied by spectrophotometry. RNAseq and Western blotting were performed t

SUBMITTER: Nandha SR 

PROVIDER: S-EPMC12406427 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature