Unraveling the role of mitochondrial dynamics in cancer stem cells: Molecular basis and therapeutic implications

Abstract

Many tumors consist of heterogeneous cell populations derived from a minority of cancer stem cells (CSCs), which possess distinct metabolic profiles that contribute to resistance against conventional anticancer therapy and increase the risk of tumor relapse. These unique CSC phenotypes are largely supported by altered mitochondrial function and turnover, regulated through continuous cycles of mitochondrial biogenesis, fission, fusion, and mitophagy. Consequently, understanding mitochondrial regulatory mechanisms in CSCs could reveal novel targets for cancer therapy. This article explores how mitochondrial dynamics contribute to CSC metabolic adaptation and drug resistance, alongside recent advances in the development of mitochondria-targeted drugs and their therapeutic usage. • Cancer stem cells are a cellular subpopulation involved in tumor aggressiveness. • They display deregulated mitochondrial mass due to changes in PGC1-α and mtDNA levels. • Mitochondrial fission and fusion proteins are overexpressed in these cells. • Mitophagy supports their self-renewal abilities and intrinsic chemoresistance. • Targeting mitochondrial dynamics represents a novel strategy for cancer eradication.