title: Molecular mechanisms regulating the mitochondrial targeting of microsomal cytochrome P450 enzymes.
abstract: Cytochrome P450 enzymes (CYPs) are a superfamily of monooxygenases found in almost all living organisms. CYPs are predominantly localized in the endoplasmic reticulum membranes as integral membrane proteins, where they metabolize a variety of endogenous and xenobiotic compounds. CYPs also reside in other subcellular compartments, including the plasma membranes and mitochondria. CYP localization in mitochondria is regulated in one of two ways: (1) direct targeting of inherent CYPs with canonical mitochondrial signals in their protein sequence after synthesis in the cytosol or (2) mitochondrial localization of microsomal CYPs after processing of the NH(2)-terminal region. Microsomal CYPs targeted to mitochondria demonstrate conventional or altered catalytic activities using electrons provided by the mitochondrial electron transport system. Mechanisms of microsomal CYP targeting to mitochondria, regulation of localization, and the implications of these in drug metabolism are described in the present review.
authors.affiliation: Department of Biochemistry, College of Veterinary Medicine, Chonnam National University, Gwangju 500-757, Republic of Korea. thahn@jnu.ac.kr
authors.forename: Taeho
authors.initials: T
authors.lastname: Ahn
authors.forename: Chul-Ho
authors.initials: CH
authors.lastname: Yun
mesh_terms: D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D003577:Cytochrome P-450 Enzyme System / Q000737:chemistry / Q000378:metabolism*; D004721:Endoplasmic Reticulum / Q000201:enzymology; D006801:Humans; D007527:Isoenzymes / Q000737:chemistry / Q000378:metabolism; D008861:Microsomes / Q000201:enzymology*; D008928:Mitochondria / Q000378:metabolism*; D008969:Molecular Sequence Data; D011499:Protein Processing, Post-Translational; D021382:Protein Sorting Signals; D021381:Protein Transport; D013379:Substrate Specificity
chemical_list: D007527:Isoenzymes; D021382:Protein Sorting Signals; D003577:Cytochrome P-450 Enzyme System