Mitochondria, OXPHOS, and Cancer Progression: A Modular View

Mitochondrial oxidative phosphorylation (OXPHOS) is an ancient metabolic process that is increasingly recognized as an important player in cancer onset, progression, and treatment resistance. In this review, we highlight the diverse biological roles of OXPHOS beyond ATP synthesis, discuss ways in which these roles interface with tumorigenesis, and consider methods to measure and manipulate OXPHOS in cancer studies. Instead of the traditional view of OXPHOS as a linear pathway with a single, defined output (i.e., ATP), we propose a more granular model of OXPHOS as a collection of interrelated functional modules that are coupled to various extents in a context-dependent manner. As a case study, we apply this modular framework to examine links between OXPHOS function and cancer metastasis. This conceptual model of OXPHOS function will support ongoing work to dissect the complex—but ultimately understandable—contributions of OXPHOS to cancer phenotypes.