FIG. 1.

The mitochondrion and its relationship to bioenergetic fluxes. Under normal conditions, neuron mitochondria may depend heavily on astrocyte-generated lactate as a carbon fuel source, and for this reason the reaction from lactate to pyruvate is explicitly indicated. The conversion of lactate to pyruvate definitely occurs in the cytosol, and some researchers believe this conversion may also occur within the mitochondrion itself. In general, though, carbon from several sources including carbohydrates, fatty acids, and amino acids can feed into the Krebs cycle. Reactions in the Krebs cycle reduce NAD⁺ to NADH and FAD to FADH₂. High-energy electrons from NADH enter the ETC at complex I, and high energy electrons from FADH₂ enter the ETC at complex II (not shown). As electrons flow through the ETC from high to low energy states, energy from those electrons is used to pump protons from the matrix to the intermembrane space and create a proton gradient. Due to electrochemical and pH gradients, protons in the intermembrane space are directed to re-access the matrix through complex V (the ATP synthase) and energy captured from this proton flux is used to phosphorylate ADP. Also shown is the mtDNA, which encodes catalytically critical parts of the complex I, III, IV, and V holoenzymes. CoQ, coenzyme; Cyt. C, cytochrome C.