Balancing glycolysis and mitochondrial OXPHOS: Lessons from the hematopoietic system and exercising muscles

•Similar energy regulatory pathways operate in seemingly distinct organ systems.•Oxygen availability is not the sole determinant of anaerobic metabolism.•Lactate is a possible mitochondrial energy source and signaling molecule.

Living organisms require a constant supply of safe and efficient energy to maintain homeostasis and to allow locomotion of single cells, tissues and the entire organism. The source of energy can be glycolysis, a simple series of enzymatic reactions in the cytosol, or a much more complex process in the mitochondria, oxidative phosphorylation (OXPHOS). In this review we will examine how does the organism balance its source of energy in two seemingly distinct and unrelated processes: hematopoiesis and exercise. In both processes we will show the importance of the metabolic program and its regulation. We will also discuss the importance of oxygen availability not as a sole determinant, but in the context of the nutrient and cellular state, and address the emerging role of lactate as an energy source and signaling molecule in health and disease.