Figure 2.

Mitochondrial metabolism in tumor progression. Mitochondria influence multiple processes that underpin tumor progression, including the proliferation of transformed cells, their resistance to adverse microenvironmental conditions, their diversification, their interaction with the tumor stroma and their dissemination toward distant anatomical sites. In particular, (1) mitochondria are major sources of ATP and building blocks for the proliferation of malignant cells; (2) progressing cancer cells display an increased threshold for mitochondrial outer membrane permeabilization (MOMP) and mitochondrial permeability transition (MPT), which renders them less sensitive to harsh microenvironmental conditions; (3) slightly supraphysiological levels of mitochondrial reactive oxygen species (ROS) foster tumor diversification (herein represented with assorted plasma membrane colors) by favoring mutagenesis; (4) different subsets of malignant cells exhibit differential metabolic profiles, which are important for their survival and function; (5) the metastatic cascade relies on optimal mitochondrial biogenesis and oxidative phosphorylation (OXPHOS), at least at the initial dissemination step. However, imbalanced ROS overproduction consequent to severe mitochondrial dysfunction is generally incompatible with tumor progression, resulting in MOMP- or MPT-driven regulated cell death or cellular senescence.