Evolutionary origin of mitochondrial cytochrome P450.
Different molecular species of cytochrome P450 (P450) are distributed between endoplasmic reticulum (microsomes) and mitochondria in animal cells. Plants and fungi have many microsomal P450s, but no mitochondrial P450 has so far been reported. To elucidate the evolutionary origin of mitochondrial P450s in animal cells, available evidence is examined, and the virtual absence of mitochondrial P450 in plants and fungi is confirmed. It is also suggested that a microsomal P450 is the ancestor of animal mitochondrial P450s. It is likely that the endoplasmic reticulum-targeting sequence at the amino-terminus of a microsomal P450 was converted to a mitochondria-targeting sequence possibly by point mutations of a few amino acid residues or by an exon-shuffling/moving event shortly after animal lineage diverged from plants and fungi in the course of evolution of eukaryotes. It is suggested that the microsome-type P450 first imported into mitochondria utilized the existing ferredoxin in the matrix to receive electrons from NADPH, retained its oxygenase activity in the mitochondria, and gradually diversified to several P450s with different substrate specificities in the course of the evolution of animals.
Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan.
Tsuneo
T
Omura
Artificial Intelligence Research Center, National Institute of Advanced Industrial Science and Technology (AIST), AIST Tokyo Waterfront Bio-IT Research Building, 2-4-7 Aomi, Koto-ku, Tokyo 135-0064, Japan.
Osamu
O
Gotoh
D000818:Animals; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D005658:Fungi / Q000378:metabolism; D008928:Mitochondria / Q000201:enzymology / Q000378:metabolism*; D010944:Plants / Q000378:metabolism
D003577:Cytochrome P-450 Enzyme System
cytochrome P450; evolution of P450; intracellular distribution of P450; microsomal P450; mitochondrial P450