Shaping fuel utilization by mitochondria

Mitochondria are central to cellular metabolism. They provide intermediate metabolites that are used in biosynthetic pathways and they process diet-derived nutrients into the energy-rich compound ATP. Mitochondrial ATP biosynthesis is a marvel of thermodynamic efficiency. Via the tricarboxylic acid cycle (TCA) and fatty acid β-oxidation, mitochondria extract electrons from dietary carbon compounds and pass them to nucleotides that ultimately deliver them to the respiratory chain complexes located in invaginations in the inner mitochondrial membrane (IMM) known as cristae. The respiratory chain complexes donate electrons in stepwise redox reactions to molecular oxygen and, with the exception of complex II, use the liberated energy to pump protons across the proton-impermeable IMM, generating a proton electrochemical gradient. This gradient is then utilized by the ATP synthase, which, in a rotary mechanism, catalyzes the formation of the high-energy γ-phosphate chemical bond between ADP and inorganic phosphate. The conversion of the chemical energy of carbon compounds into a physical, vectorial form of energy (the electrochemical gradient) maximizes the yield of the ATP biosynthetic process and is perhaps one of the foundations of life as we know it.