title: Mitochondrial fatty acid synthesis--an adopted set of enzymes making a pathway of major importance for the cellular metabolism.
abstract: The highly conserved fatty acid de novo synthesis pathway in mitochondria proceeds in an acyl carrier protein-dependent manner through a discrete set of enzymes. Saccharomyces cerevisiae has served as a model for studies of mitochondrial fatty acid synthesis type II (FAS II) and as a template for identification of mammalian components. Inactivation of mitochondrial FAS II in yeast results in respiratory deficiency and loss of cytochromes. The pathway produces the octanoyl-ACP substrate for lipoic acid synthesis, but several pieces of evidence indicate that it is capable of the generation of longer fatty acids. A number of structures of mitochondrial FAS II enzymes have been published in the past few years, allowing for a comparison with their prokaryotic counterparts, several of which have been described as promising targets for antibiotics. Recently, novel links between mitochondrial FAS and RNA processing in yeast and vertebrates have been reported. In S. cerevisiae, deficiency in mitochondrial FAS results in failure of maturation of mitochondrial RNAse P, while, in mammals, mitochondrial 3-hydroxyacyl thioester dehydratase and the RPP14 subunit of RNase P are encoded by the same bicistronic transcript. The first publications linking mitochondrial FAS II to disease states in mammals are emerging.
authors.affiliation: Department of Biochemistry and Biocenter Oulu, University of Oulu, P.O.B. 3000, FI-90014 Oulu, Finland. kalervo.hiltunen@oulu.fi
authors.forename: J Kalervo
authors.initials: JK
authors.lastname: Hiltunen
authors.forename: Zhijun
authors.initials: Z
authors.lastname: Chen
authors.forename: Antti M
authors.initials: AM
authors.lastname: Haapalainen
authors.forename: Rik K
authors.initials: RK
authors.lastname: Wierenga
authors.forename: Alexander J
authors.initials: AJ
authors.lastname: Kastaniotis
mesh_terms: D064431:3-Oxoacyl-(Acyl-Carrier-Protein) Reductase; D051080:Acyl-Carrier Protein S-Malonyltransferase / Q000737:chemistry / Q000378:metabolism; D000429:Alcohol Oxidoreductases / Q000737:chemistry / Q000378:metabolism; D001426:Bacterial Proteins / Q000737:chemistry / Q000378:metabolism; D004746:Enoyl-CoA Hydratase / Q000737:chemistry / Q000378:metabolism; D044943:Fatty Acid Desaturases / Q000737:chemistry / Q000378:metabolism; D054889:Fatty Acid Synthase, Type II / Q000378:metabolism; D005227:Fatty Acids / Q000096:biosynthesis* / Q000378:metabolism; D008928:Mitochondria / Q000201:enzymology* / Q000378:metabolism; D043262:Ribonuclease P / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000201:enzymology; D017855:Transferases (Other Substituted Phosphate Groups) / Q000737:chemistry / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; D005227:Fatty Acids; C082662:phosphopantetheinyl transferase; D000429:Alcohol Oxidoreductases; D064431:3-Oxoacyl-(Acyl-Carrier-Protein) Reductase; D044943:Fatty Acid Desaturases; D051080:Acyl-Carrier Protein S-Malonyltransferase; D017855:Transferases (Other Substituted Phosphate Groups); D043262:Ribonuclease P; D004746:Enoyl-CoA Hydratase; D054889:Fatty Acid Synthase, Type II