title: The mitochondrial acyl carrier protein (ACP) coordinates mitochondrial fatty acid synthesis with iron sulfur cluster biogenesis.
abstract: Mitochondrial fatty acid synthesis (FASII) and iron sulfur cluster (FeS) biogenesis are both vital biosynthetic processes within mitochondria. In this study, we demonstrate that the mitochondrial acyl carrier protein (ACP), which has a well-known role in FASII, plays an unexpected and evolutionarily conserved role in FeS biogenesis. ACP is a stable and essential subunit of the eukaryotic FeS biogenesis complex. In the absence of ACP, the complex is destabilized resulting in a profound depletion of FeS throughout the cell. This role of ACP depends upon its covalently bound 4'-phosphopantetheine (4-PP)-conjugated acyl chain to support maximal cysteine desulfurase activity. Thus, it is likely that ACP is not simply an obligate subunit but also exploits the 4-PP-conjugated acyl chain to coordinate mitochondrial fatty acid and FeS biogenesis.
authors.affiliation: Department of Biochemistry, University of Utah School of Medicine, Salt Lake City, United States.
authors.forename: Jonathan G
authors.identifier: 0000-0002-8931-852X
authors.initials: JG
authors.lastname: Van Vranken
authors.affiliation: Department of Biochemistry, University of Utah School of Medicine, Salt Lake City, United States.|Department of Medicine, University of Utah School of Medicine, Salt Lake City, United States.
authors.forename: Mi-Young
authors.initials: MY
authors.lastname: Jeong
authors.affiliation: Department of Biochemistry, University of Utah School of Medicine, Salt Lake City, United States.
authors.forename: Peng
authors.initials: P
authors.lastname: Wei
authors.affiliation: Department of Biochemistry, University of Utah School of Medicine, Salt Lake City, United States.
authors.forename: Yu-Chan
authors.initials: YC
authors.lastname: Chen
authors.affiliation: Department of Cell Biology, Harvard University School of Medicine, Boston, United States.
authors.forename: Steven P
authors.initials: SP
authors.lastname: Gygi
authors.affiliation: Department of Biochemistry, University of Utah School of Medicine, Salt Lake City, United States.|Department of Medicine, University of Utah School of Medicine, Salt Lake City, United States.
authors.forename: Dennis R
authors.identifier: 0000-0003-1160-1189
authors.initials: DR
authors.lastname: Winge
authors.affiliation: Department of Biochemistry, University of Utah School of Medicine, Salt Lake City, United States.|Howard Hughes Medical Institute, University of Utah School of Medicine, Salt Lake City, United States.
authors.forename: Jared
authors.identifier: 0000-0002-2710-9765
authors.initials: J
authors.lastname: Rutter
mesh_terms: D000213:Acyl Carrier Protein / Q000378:metabolism*; D005227:Fatty Acids / Q000378:metabolism*; D058085:Iron Compounds / Q000378:metabolism*; D008928:Mitochondria / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000378:metabolism; D013457:Sulfur Compounds / Q000378:metabolism*
chemical_list: D000213:Acyl Carrier Protein; D005227:Fatty Acids; D058085:Iron Compounds; D013457:Sulfur Compounds
keywords: S. cerevisiae; acyl carrier protein; biochemistry; iron sulfur cluster biogenesis; mitochondrial fatty acid synthesis; mouse