Fig. 2.

Metabolic determinants of cell fitness in competition.

A. Protein synthesis capacity. Winner cells display increased protein synthesis rates compared to loser cells. This may be due to increased Myc expression or higher mTOR pathway activity in winner cells, or to ribosomal protein mutations in loser cells.

B. Glycolytic Flux. Winner cells display increased glycolytic flux relative to loser cells. This may be driven by transcriptional regulation of metabolic genes by transcription factors such as Myc and p53. Glucose availability in the microenvironment may also affect glycolysis, with winner cells displaying increased uptake of glucose.

C. Mitochondria Function. Loser cells may display impaired mitochondria function, resulting in decreased mitochondrial membrane potential (MMP), ATP production and mitophagy. Reactive oxygen species (ROS) production may also be elevated in loser cells with impaired mitochondrial function.