Heme biosynthesis begins in the mitochondrial matrix by the condensation of glycine and succinyl-CoA to produce 5-aminolevulinate (5-ALA). Following its transport to the cytosol, 5-ALA is used to form the porphyrinogen core which is further modified to produce coproporphyrinogen III. In the mitochondrial intermembrane space, coproporphyrinogen III is converted into protoporphyrinogen which is then transported across the mitochondrial inner membrane probably via an ATP-dependent transporter. In the mitochondrial matrix, ferrous iron is inserted into the porphyrin ring, resulting in heme b which can be further modified to produce heme o and heme a, all of which function as a prosthetic group in various proteins. (Adapted from PMID:38888238.)