Figure 1.

Simplified depiction of oxidisable substrate provision and usage by the mitochondria. The generalised “flow” of substrate molecules derived from glucose, fatty acids or amino acids is represented by arrows colour-coded green, blue and red, respectively. Reducing equivalents are denoted by purple. Processes are italicised. Glucose may be catabolised by glycolysis in order to provision the mitochondria with pyruvate, converted by pyruvate dehydrogenase (PDH) to acetyl CoA for entry into the TCA cycle. Fatty acid β-oxidation also provides acetyl CoA for the TCA cycle, by the catabolism of lipids rather than carbohydrates. The means by which amino acids may be similarly utilised are diverse and are described as appropriate throughout the text. However, we have highlighted glutamine usage in this figure due to its importance. Glutamine may be converted to glutamate by glutaminase. Glutamate may be converted to α-KG by glutamate dehydrogenase (GLUD1) for entry into the TCA cycle, or to aspartate by mitochondrial aspartate aminotransferase (GOT2) which is utilised in cellular redox balancing and TCA cycle anaplerosis, thereby providing both reducing equivalents for OXPHOS and intermediates for the TCA cycle. Reducing equivalents resultant from these myriad processes can deposit electrons into the electron transport chain to facilitate generation of the proton-motive force which drives ATP synthesis.