ACP1 (YKL192C) encodes the mitochondrial acyl carrier protein, a small acidic protein that is activated by attachment of a 4'-phosphopantetheine (4-PP) prosthetic group by the mitochondrial phosphopantetheinyl transferase Ppt2. Holo-Acp1 carries malonyl and growing acyl chains as thioesters between the dissociated enzymes of mitochondrial type II fatty acid synthesis (FAS II: Mct1, Cem1, Oar1, Htd2, Etr1), whose main product, octanoyl-ACP, is the precursor for lipoic acid synthesis and protein lipoylation of mitochondrial 2-oxoacid dehydrogenases and the glycine cleavage system; acp1 null mutants retain only 5-10% of wild-type lipoic acid and are respiratory deficient. Acp1 is also a stable, essential subunit of the mitochondrial iron-sulfur cluster assembly complex, where its acyl-4-PP chain binds Isd11 and stabilises the Nfs1-Isd11 cysteine desulfurase, coupling FAS II to Fe-S cluster biogenesis. Unlike mammalian and Neurospora ACPs, yeast Acp1 is not a Complex I subunit, because S. cerevisiae lacks Complex I.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0000035 acyl binding | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: PAINT acyl binding from E. coli AcpP and M. tuberculosis AcpM. Acyl chains are bound covalently as thioesters to the 4-PP group of holo-ACP; the term is true but is subsumed by acyl carrier activity, which describes the function. |
| GO:0000036 acyl carrier activity | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT node PTN000466551 seeded by bacterial AcpP/AcpM, plant mitochondrial ACPs and a trypanosome mitochondrial ACP. Acp1 is the yeast mitochondrial FAS II carrier; sound inheritance of the core MF. Supporting Evidence: PMID:9187370 Mitochondrial ACP is therefore suggested to be involved with the biosynthesis of octanoate, a precursor to lipoic acid. |
| GO:0000036 acyl carrier activity | ISS PMID:8394042 DNA sequence analysis of the YCN2 region of chromosome XI in... | ACCEPT | Summary: Sequence similarity to Neurospora mitochondrial ACP (P11943) noted when the ORF was sequenced. Consistent with the later genetic evidence (lipoate deficiency of acp1 mutants) and the FAS II role. Core MF. Supporting Evidence: PMID:8394042 a mitochondrial acyl-carrier protein |
| GO:0005739 mitochondrion | HDA PMID:14576278 The proteome of Saccharomyces cerevisiae mitochondria. | ACCEPT | Summary: Sickmann et al. 2003 mitochondrial proteome detects Acp1. Correct. |
| GO:0005739 mitochondrion | HDA PMID:16823961 Toward the complete yeast mitochondrial proteome: multidimen... | ACCEPT | Summary: Reinders et al. 2006 mitochondrial proteome detects Acp1. Correct. |
| GO:0005739 mitochondrion | HDA PMID:24769239 Quantitative variations of the mitochondrial proteome and ph... | ACCEPT | Summary: Renvoise et al. 2014 quantitative mitochondrial proteome detects Acp1. Correct. |
| GO:0005739 mitochondrion | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT is_active_in mitochondrion on the eukaryotic mitochondrial ACP node (PTN000466616), grounded on yeast, human and plant mitochondrial ACPs. Correct. |
| GO:0005739 mitochondrion | IEA GO_REF:0000044 | ACCEPT | Summary: UniProt SubCell (SL-0173) mapping. Correct; the matrix would be more precise. Supporting Evidence: file:yeast/ACP1/ACP1-uniprot.txt SUBCELLULAR LOCATION: Mitochondrion. |
| GO:0005739 mitochondrion | NAS PMID:26342079 Mapping Key Residues of ISD11 Critical for NFS1-ISD11 Subcom... | ACCEPT | Summary: Author statement in an ISD11/NFS1 study (Saha et al. 2015) placing Acp1 in mitochondria with the Fe-S assembly machinery. Correct, redundant with direct evidence. |
| GO:0006633 fatty acid biosynthetic process | IEA GO_REF:0000120 | ACCEPT | Summary: InterPro IPR003231 (ACP) / UniPathway fatty acid biosynthesis mapping. Correct: Acp1 is the carrier of mitochondrial FAS II, whose main product is octanoyl-ACP. Supporting Evidence: PMID:27540631 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. |
| GO:0009107 obsolete lipoate biosynthetic process | IMP PMID:9187370 Mitochondrial acyl carrier protein is involved in lipoic aci... | MODIFY | Summary: Brody et al. 1997: acp1 deletion leaves only 5-10% of wild-type lipoic acid and causes respiratory deficiency, implicating mitochondrial ACP in octanoate synthesis for lipoic acid. The term 'lipoate biosynthetic process' (GO:0009107) is obsolete and GO designates protein lipoylation (GO:0009249) as its replacement. Octanoyl-Acp1 is the acyl donor for the first step of mitochondrial protein lipoylation, so Acp1 participates as the carrier. Proposed replacements: protein lipoylation Supporting Evidence: PMID:9187370 The resulting acp1-deficient mutants had only 5-10% of the wild-type lipoic acid content remaining, and exhibited a respiratory-deficient phenotype. |
| GO:0016226 iron-sulfur cluster assembly | IMP PMID:27540631 The mitochondrial acyl carrier protein (ACP) coordinates mit... | ACCEPT | Summary: Van Vranken et al. 2016: Acp1 is a stable subunit of the yeast ISU complex (Nfs1-Isd11-Isu1); Acp1 knockdown destabilises Nfs1-Isd11 and depletes FeS cluster proteins, and the 4-PP acyl chain is required. Acp1 contributes structurally to the cysteine desulfurase step, so it participates in Fe-S cluster assembly. Core process (second role). Supporting Evidence: PMID:27540631 Thus, in the absence of Acp1, the Nfs1-Isd11 complex is destabilized, most likely causing a loss of cysteine desulfurase activity. |
| GO:0016226 iron-sulfur cluster assembly | NAS PMID:34199378 Molecular Details of the Frataxin-Scaffold Interaction durin... | ACCEPT | Summary: Review-style statement about the NFS1/ISD11/ACP complex in Fe-S assembly (largely human-focused). Correct and consistent with the yeast IMP evidence. Supporting Evidence: PMID:34199378 An additional protein, the acyl-carrier protein (ACP1 in humans) closely interacts with ISD11 to form the NFS1/ISD11/ACP1 (NIA) protein complex. |
| GO:0099128 mitochondrial [2Fe-2S] assembly complex | IEA GO_REF:0000117 | ACCEPT | Summary: ARBA00087777 assignment of membership in the mitochondrial [2Fe-2S] assembly complex. Correct, supported experimentally in yeast. |
| GO:0099128 mitochondrial [2Fe-2S] assembly complex | IPI PMID:27540631 The mitochondrial acyl carrier protein (ACP) coordinates mit... | ACCEPT | Summary: Acp1 co-immunoprecipitates with Nfs1, Isd11 and Isu1 (SGD:S000000522, S000006056, S000007237) and co-purifies with intact Nfs1-Isd11 on BN-PAGE. Correct. Supporting Evidence: PMID:27540631 Taken together these data demonstrate that Acp1 is a stable and evolutionarily conserved subunit of the ISU complex with Nfs1, Isd11, and Isu1. |
| GO:1990229 iron-sulfur cluster assembly complex | NAS PMID:34199378 Molecular Details of the Frataxin-Scaffold Interaction durin... | ACCEPT | Summary: Iron-sulfur cluster assembly complex (parent of the mitochondrial [2Fe-2S] assembly complex) stated in a review. Correct but less precise than GO:0099128. |
Loading supporting content…
Download this section (compressed HTML)Q: Which acyl-chain lengths on Acp1 are bound in the Isd11 complex in vivo, and does the acylation state signal mitochondrial acetyl-CoA/FAS II status to Fe-S biogenesis?
Q: Does yeast Acp1 interact with other LYR-motif proteins (as mammalian ACP does) despite the absence of Complex I in S. cerevisiae?
Experiment: Mass spectrometry of acyl-Acp1 species co-purifying with Nfs1-Isd11 versus free Acp1 under fermentative and respiratory growth, combined with FAS II mutants (htd2, etr1).
Type: proteomics
Mitochondrial matrix acyl carrier protein; involved in biosynthesis of octanoate, which is a precursor to lipoic acid; coordinates mitochondrial fatty acid and iron sulfur cluster metabolism; activated by phosphopantetheinylation catalyzed by Ppt2p
Loading supporting content…
Download this section (compressed HTML)Loading supporting content…
Download this section (compressed HTML)