ETR1 (YBR026C; also MRF1') encodes the mitochondrial 2-enoyl thioester reductase of type II fatty acid synthesis (FAS II), a zinc-independent member of the medium-chain dehydrogenase/reductase (MDR) superfamily (quinone oxidoreductase subfamily) orthologous to human MECR. Etr1 catalyses the NADPH-dependent reduction of trans-2-enoyl-ACP to saturated acyl-ACP, the final step of each FAS II elongation cycle; in vitro it also reduces CoA thioesters. Etr1 is located in the mitochondrial matrix. Deletion causes respiratory deficiency, low cytochrome content and rudimentary mitochondria, which can be complemented only by mitochondrially targeted reductases, including the structurally unrelated E. coli FabI, showing that mitochondrial enoyl-ACP reductase activity is what is required. Overexpression enlarges mitochondria. Etr1 was first described as a single-stranded ARS-binding protein, a nuclear function later judged incorrect.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005739 mitochondrion | HDA PMID:14576278 The proteome of Saccharomyces cerevisiae mitochondria. | ACCEPT | Summary: Sickmann et al. 2003 mitochondrial proteome detects Etr1. Correct. |
| GO:0005739 mitochondrion | HDA PMID:16823961 Toward the complete yeast mitochondrial proteome: multidimen... | ACCEPT | Summary: Reinders et al. 2006 mitochondrial proteome detects Etr1. Correct. |
| GO:0005739 mitochondrion | HDA PMID:24769239 Quantitative variations of the mitochondrial proteome and ph... | ACCEPT | Summary: Renvoise et al. 2014 mitochondrial proteome detects Etr1. Correct. |
| GO:0005739 mitochondrion | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT is_active_in mitochondrion on the MECR node (PTN000190628), seeded by human MECR, rat Mecr, Drosophila, trypanosomatid and yeast Etr1. Sound. |
| GO:0005739 mitochondrion | IDA PMID:11509667 Candida tropicalis Etr1p and Saccharomyces cerevisiae Ybr026... | ACCEPT | Summary: Immunolocalisation and in vivo targeting showed Ybr026p is predominantly mitochondrial. Correct. Supporting Evidence: PMID:11509667 Immunolocalization and in vivo targeting experiments showed these proteins to be predominantly mitochondrial. |
| GO:0005759 mitochondrial matrix | EXP PMID:11509667 Candida tropicalis Etr1p and Saccharomyces cerevisiae Ybr026... | ACCEPT | Summary: Matrix localisation curated from Torkko et al. 2001 (UniProt also cites this and the mitochondrial proteome for matrix). Core location of the FAS II reductase. Supporting Evidence: file:yeast/ETR1/ETR1-uniprot.txt SUBCELLULAR LOCATION: Mitochondrion matrix |
| GO:0005759 mitochondrial matrix | IEA GO_REF:0000044 | ACCEPT | Summary: UniProt SubCell (SL-0170 mitochondrion matrix) mapping. Correct. |
| GO:0006631 fatty acid metabolic process | IBA GO_REF:0000033 | TOO GENERAL | Summary: PAINT fatty acid metabolic process on the MECR node. Correct but broad; fatty acid biosynthetic process is the precise process. |
| GO:0006633 fatty acid biosynthetic process | IMP PMID:11509667 Candida tropicalis Etr1p and Saccharomyces cerevisiae Ybr026... | ACCEPT | Summary: The etr1 (ybr026c) respiratory defect is complemented by mitochondrially targeted E. coli FabI, the bacterial FAS II enoyl-ACP reductase, placing Etr1 in mitochondrial FAS. Core BP. Supporting Evidence: PMID:11509667 The mutant phenotype was also complemented by a mitochondrially targeted FabI protein from Escherichia coli. |
| GO:0009060 aerobic respiration | IMP PMID:11509667 Candida tropicalis Etr1p and Saccharomyces cerevisiae Ybr026... | KEEP AS NON CORE | Summary: ybr026c deletion causes a respiration-deficient phenotype with low cytochromes. Etr1 does not perform a step of aerobic respiration; the defect arises indirectly via loss of FAS II products (octanoyl-ACP for lipoylation of the 2-oxoacid dehydrogenases, and acyl-ACP for Fe-S/respiratory complex assembly). Real phenotype, pleiotropic consequence; non-core. Supporting Evidence: PMID:11509667 deletion of the S. cerevisiae YBR026c gene resulted in rudimentary mitochondria with decreased contents of cytochromes and a respiration-deficient phenotype |
| GO:0141148 enoyl-[acyl-carrier-protein] reductase (NADPH) activity | IDA PMID:11509667 Candida tropicalis Etr1p and Saccharomyces cerevisiae Ybr026... | ACCEPT | Summary: Torkko et al. 2001 characterised Ybr026p as an NADPH-dependent 2-enoyl thioester reductase (UniProt cites this paper as experimental evidence for its activity on 2-enoyl-CoA substrates), and complementation by mitochondrial E. coli FabI supports the enoyl-ACP reductase role in vivo. Core MF. Supporting Evidence: PMID:11509667 We conclude that Etr1p and Ybr026p are novel 2-enoyl thioester reductases required for respiration and the maintenance of the mitochondrial compartment, putatively acting in mitochondrial synthesis of fatty acids. |
| GO:0141148 enoyl-[acyl-carrier-protein] reductase (NADPH) activity | IEA GO_REF:0000120 | ACCEPT | Summary: RHEA:22564 / EC 1.3.1.104 mapping from the UniProt catalytic activity. Correct. |
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Download this section (compressed HTML)Q: Is the reported ARS single-stranded DNA binding (PMID:8195160) attributable to Etr1 at all, or an artefact of the original screen?
Q: What is the physiological significance of Etr1 activity on CoA thioesters, e.g. in mitochondrial chain elongation independent of ACP?
Experiment: Measure lipoylation of Lat1/Kgd2 and Fe-S enzyme activities in etr1 cells complemented with catalytically dead versus active Etr1 to separate catalytic and structural requirements.
Type: genetics
2-enoyl thioester reductase; member of the medium chain dehydrogenase/reductase family; localized to mitochondria, where it has a probable role in fatty acid synthesis; human MECR functionally complements the respiratory growth defect of the null mutant
UniProt P38071; module type_ii_fatty_acid_synthesis (enoyl reductase annoton, GO:0141148).
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