Figure 1.

Main features of mitochondrial metabolism. Flux of metabolites including the respiratory substrates pyruvate, adenosine diphosphate (ADP), and inorganic phosphate (Pi) and certain amino acids, cross the outer mitochondrial membrane occurs through voltage dependent anion channels (VDAC). Catabolism of respiratory substrates in the Krebs cycle generates 1,4-dihydronicotinamide adenine dinucleotide (NADH) and dihydroflavine-adenine nucleotide (FADH₂), which fuel the electron transport chain (ETC; complexes I–IV) to support oxidative phosphorylation. The Krebs cycle also produces metabolic intermediaries released to the cytosol for the biosynthesis of proteins and lipids. Proton pumping by the respiratory chain across inner mitochondrial membrane (IMM) generates mitochondrial ΔΨ. Protons moving back across MIM into the matrix drive ATP synthesis from ADP and Pi by the F₁F₀-ATP synthase (complex V). Mitochondrial ATP is exported from the matrix by the adenine nucleotide transporter (ANT) and released to the cytosol through VDAC. Flow of electrons through complexes I, II, and III also generates reactive oxygen species. AcCoA, acetyl CoA; α-KG, alpha ketoglutarate; IMM, inner mitochondrial membrane; OMM, outer mitochondrial membrane; and ROS, reactive oxygen species.