Fig. 4

Mitochondrial homeostasis and cancer stem cell stemness. A PGC-1α or its cofactor ERRα increases mitochondrial biogenesis, which further promotes the maintenance of the CSC phenotype. Azithromycin, doxycycline, and tigecycline block mitochondrial biogenesis by targeting mitochondrial ribosomes 39S and 28S and then inhibit CSC self-renewal capability. In addition, the selective PGC-1α inhibitor SR-18292 or ERRα inverse agonist XCT790 downregulates the expression of stemness genes and reduces the ratio of CSCs. B AMPK-FIS1 signaling promotes mitophagy, thereby enhancing CSC self-renewal by inhibiting ROS production. CCCP increases CSC ratios by recruiting PINK1 and enhancing mitophagy-mediated removal of phosphorylated p53 and then increases NANOG expression. In contrast, the combination of melatonin and verteporfin reduces CSC stemness by inhibiting the expression of PINK1/Parkin, while mefloquine hydrochloride reduces the ratio of colon CSCs by inhibiting mitophagy and lysosomal activity. In addition, ¹⁸⁸Re-liposomes reduced the protein levels of mitophagy markers, which further decreased the function of CSCs. CSC Cancer stem cell, AMPK Adenosine 5'-monophosphate-activated protein, FIS1 Fission factor 1, CCCP Carbonyl cyanide chlorophenylhydrazone, PINK1 PTEN-induced kinase 1