# MECR

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> License: Creative Commons Attribution-ShareAlike 4.0 International (https://creativecommons.org/licenses/by-sa/4.0/)

**Mitochondrial trans-2-enoyl-CoA reductase** (**MECR**) is an [enzyme](/source/Enzyme) that in humans is encoded by the *MECR* [gene](/source/Gene).[1] It belongs to the [enzyme class](/source/Enzyme_classification) of [oxidoreductases](/source/Oxidoreductase) and catalyzes the last step of [mitochondrial fatty acid synthesis](/source/Mitochondrial_fatty_acid_synthesis) (mtFAS).[2] In doing so, MECR makes the fatty acyl chain bound to [mitochondrial acyl carrier protein](/source/Mitochondrial_acyl_carrier_protein) (mtACP) available again for elongation.[3] MECR thereby contributes to mitochondrial respiration and [oxidative phosphorylation](/source/Oxidative_phosphorylation).[4] Beyond its [mitochondrial](/source/Mitochondrion) role, a [cytosolic](/source/Cytosol) and [nuclear](/source/Cell_nucleus) [isoform](/source/Protein_isoform) (cMECR) has been linked to [PPARα](/source/Peroxisome_proliferator-activated_receptor_alpha)-dependent [transcription](/source/Transcription_(biology)).[5] Pathogenic [variants](/source/Mutation) in the *MECR* gene cause [MEPAN syndrome](/source/MEPAN_syndrome).[4]

## Structure

The *MECR* gene is located on [chromosome 1](/source/Chromosome_1) at [locus](/source/Locus_(genetics)) p35.3 and contains 18 [exons](/source/Exon).[2] Through [alternative splicing](/source/Alternative_splicing), it produces nine protein-coding [mRNA](/source/Messenger_RNA) [transcripts](/source/Transcription_(biology)), which encode five isoforms of mitochondrial trans-2-enoyl-CoA reductase (MECR).[2] The cMECR isoform lacks the [N-terminal](/source/N-terminus) [mitochondrial targeting sequence](/source/Mitochondrial_targeting_sequence) and localizes to the cytosol and nucleus.[5]

MECR forms a [dimer](/source/Protein_dimer) with a bent substrate-binding cavity between the two [monomers](/source/Monomer) that accommodates acyl substrates with [carbon](/source/Carbon) chain lengths from C4 to C16.[6][7]

## Reaction

The reaction catalyzed by MECR can be summarized as follows:

- [trans-2-enoyl-mtACP](/source/Trans-2-enoyl-mtACP) + [NADPH](/source/Nicotinamide_adenine_dinucleotide_phosphate) + [H+](/source/Hydrogen_ion) → [acyl-mtACP](/source/Acyl-mtACP) + [NADP+](/source/Nicotinamide_adenine_dinucleotide_phosphate)

## Function

The *MECR* gene encodes mitochondrial trans-2-enoyl-CoA reductase, which catalyzes the last step of mitochondrial fatty acid synthesis (mtFAS).[4] [Condensation](/source/Condensation_reaction) in mtFAS produces an [unsaturated](/source/Unsaturated_fatty_acid) fatty acyl chain bound to mtACP.[3] It must undergo [reduction](/source/Reduction_(chem)) and [dehydration](/source/Dehydration_reaction) reactions to become [saturated](/source/Saturated_Fatty_Acid), making it available again for the next elongation cycle.[3] MECR completes this process by reducing the [trans](/source/Cis%E2%80%93trans_isomerism) [double bond](/source/Double_bond) between carbon atoms 2 and 3, yielding a [saturated](/source/Saturated_Fatty_Acid) acyl-mtACP species.[8] [NADPH](/source/Nicotinamide_adenine_dinucleotide_phosphate), whose availability in mitochondria depends on [NADK2](/source/NADK2), provides the required reducing power.[9] Through repeated elongation cycles, mitochondrial fatty acid synthesis generates acyl-mtACP species with chain lengths from C2 to C16.[10] [Octanoyl-mtACP](/source/Octanoyl-mtACP) (C8) serves as the [precursor](/source/Precursor_(chemistry)) for [lipoic acid](/source/Lipoic_acid) biosynthesis and subsequent [protein lipoylation](/source/Protein_lipoylation), which is essential for several mitochondrial enzyme complexes, including the [pyruvate dehydrogenase complex](/source/Pyruvate_dehydrogenase_complex), the [2-oxoglutarate dehydrogenase complex](/source/Oxoglutarate_dehydrogenase_complex), the [branched-chain alpha-keto acid dehydrogenase complex](/source/Branched-chain_alpha-keto_acid_dehydrogenase_complex), the [2-oxoadipate dehydrogenase complex](/source/2-oxoadipate_dehydrogenase_complex), and the [glycine cleavage system](/source/Glycine_cleavage_system).[11] Longer-chain acyl-mtACP species interact with [LYRM proteins](/source/LYRM_protein) that are required for [iron–sulfur cluster](/source/Iron%E2%80%93sulfur_cluster) biogenesis and [respiratory-chain](/source/Respiratory_chain) assembly.[11] In addition, mtFAS has been linked to mitochondrial [translation](/source/Translation_(biology)) and to levels of [polyamines](/source/Polyamine), including [spermidine](/source/Spermidine) and [spermine](/source/Spermine), as well as bioactive lipids such as [lysophospholipids](/source/Lysophospholipids) and [sphingolipids](/source/Sphingolipid).[9][6]

MECR has also been reported to bind [transcription factors](/source/Transcription_factor) of the [PPAR](/source/PPAR) family and activate [transcription](/source/Transcription_(biology)), suggesting a possible link between [nuclear](/source/Cell_nucleus) gene regulation and mtFAS.[4]

## Clinical significance

Pathogenic variants in the *MECR* gene cause [MEPAN syndrome](/source/MEPAN_syndrome), a rare [autosomal recessive](/source/Autosomal_recessive) mitochondrial [metabolic disorder](/source/Metabolic_disorder) characterized by childhood-onset [dystonia](/source/Dystonia), [optic atrophy](/source/Optic_atrophy), and [basal ganglia](/source/Basal_ganglia) signal abnormalities on [MRI](/source/Magnetic_resonance_imaging).[12] A later-onset [phenotype](/source/Phenotype_(clinical_medicine)) with [LHON](/source/Leber's_hereditary_optic_neuropathy)-like [optic neuropathy](/source/Optic_neuropathy) but without movement disorder or basal ganglia signal abnormalities has also been reported.[13][14][15]

## See also

- [ACSF3](/source/ACSF3)
- [MCAT](/source/MCAT_(gene))
- [Combined malonic and methylmalonic aciduria](/source/Combined_malonic_and_methylmalonic_aciduria) (CMAMMA)

## References

1. ["Gene symbol report | HUGO Gene Nomenclature Committee"](https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:19691). *www.genenames.org*. Retrieved 2026-05-19.

1. ["MECR mitochondrial trans-2-enoyl-CoA reductase \[Homo sapiens (human)\] - Gene - NCBI"](https://www.ncbi.nlm.nih.gov/gene/51102). *www.ncbi.nlm.nih.gov*. Retrieved 2026-05-19.

1. Nowinski, Sara M; Solmonson, Ashley; Rusin, Scott F; Maschek, J Alan; Bensard, Claire L; Fogarty, Sarah; Jeong, Mi-Young; Lettlova, Sandra; Berg, Jordan A; Morgan, Jeffrey T; Ouyang, Yeyun; Naylor, Bradley C; Paulo, Joao A; Funai, Katsuhiko; Cox, James E (2020-08-17). "Mitochondrial fatty acid synthesis coordinates oxidative metabolism in mammalian mitochondria". *eLife*. **9**. [doi:10.7554/eLife.58041](https://doi.org/10.7554/eLife.58041). [ISSN 2050-084X](https://www.worldcat.org/issn/2050-084X). [PMC 7470841](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7470841). [PMID 32804083](https://pubmed.ncbi.nlm.nih.gov/32804083)

1. Murdock, Deborah G.; Janssen, Kevin A.; Keller, Kierstin; Mitchell, Katherine L.; Beauplan, Maina; O'Brien, William T.; D'Alessandro, Lia; Haltom, Jeffrey A.; Wallace, Douglas C. (2025-10-07). ["A mouse model of MEPAN demonstrates a role for mitochondrial fatty acid synthesis in iron–sulfur cluster and supercomplex formation"](https://pnas.org/doi/10.1073/pnas.2506761122). *Proceedings of the National Academy of Sciences*. **122** (40). [doi:10.1073/pnas.2506761122](https://doi.org/10.1073/pnas.2506761122). [ISSN 0027-8424](https://www.worldcat.org/issn/0027-8424). [PMC 12519216](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12519216). [PMID 41021813](https://pubmed.ncbi.nlm.nih.gov/41021813)

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1. Clay, Hayley B.; Parl, Angelika K.; Mitchell, Sabrina L.; Singh, Larry; Bell, Lauren N.; Murdock, Deborah G. (2016-03-10). "Altering the Mitochondrial Fatty Acid Synthesis (mtFASII) Pathway Modulates Cellular Metabolic States and Bioactive Lipid Profiles as Revealed by Metabolomic Profiling". *PLOS ONE*. **11** (3). Peterson, Jonathan (ed.). [doi:10.1371/journal.pone.0151171](https://doi.org/10.1371/journal.pone.0151171). [ISSN 1932-6203](https://www.worldcat.org/issn/1932-6203). [PMC 4786287](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4786287). [PMID 26963735](https://pubmed.ncbi.nlm.nih.gov/26963735)

1. Rahman, M. Tanvir; Koski, M. Kristian; Panecka-Hofman, Joanna; Schmitz, Werner; Kastaniotis, Alexander J.; Wade, Rebecca C.; Wierenga, Rik K.; Hiltunen, J. Kalervo; Autio, Kaija J. (2023-02-04). "An engineered variant of MECR reductase reveals indispensability of long-chain acyl-ACPs for mitochondrial respiration". *Nature Communications*. **14** (1). [doi:10.1038/s41467-023-36358-7](https://doi.org/10.1038/s41467-023-36358-7). [ISSN 2041-1723](https://www.worldcat.org/issn/2041-1723). [PMC 9899272](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9899272). [PMID 36739436](https://pubmed.ncbi.nlm.nih.gov/36739436)

1. Wedan, Riley J.; Longenecker, Jacob Z.; Nowinski, Sara M. (January 2024). "Mitochondrial fatty acid synthesis is an emergent central regulator of mammalian oxidative metabolism". *Cell Metabolism*. **36** (1): 36–47. [doi:10.1016/j.cmet.2023.11.017](https://doi.org/10.1016/j.cmet.2023.11.017). [PMC 10843818](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10843818). [PMID 38128528](https://pubmed.ncbi.nlm.nih.gov/38128528)

1. Wedan, Riley J. & Nowinski, Sara M. (July 2025). "Powering the powerhouse: Mitochondrial NADPH propels oxidative metabolism". *Cell Chemical Biology*. **32** (7): 902–904. [doi:10.1016/j.chembiol.2025.06.006](https://doi.org/10.1016/j.chembiol.2025.06.006). [PMC 12507123](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12507123). [PMID 40680726](https://pubmed.ncbi.nlm.nih.gov/40680726)

1. Kim, Dohun; Kesavan, Rushendhiran; Ryu, Kevin; Dey, Trishna; Marckx, Austin; Menezes, Cameron; Praharaj, Prakash P.; Morley, Stewart; Ko, Bookyung; Soflaee, Mona H.; Tom, Harrison J.; Brown, Harrison; Vu, Hieu S.; Tso, Shih-Chia; Brautigam, Chad A. (May 2025). "Mitochondrial NADPH fuels mitochondrial fatty acid synthesis and lipoylation to power oxidative metabolism". *Nature Cell Biology*. **27** (5): 790–800. [doi:10.1038/s41556-025-01655-4](https://doi.org/10.1038/s41556-025-01655-4). [ISSN 1465-7392](https://www.worldcat.org/issn/1465-7392). [PMC 12331256](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12331256). [PMID 40258949](https://pubmed.ncbi.nlm.nih.gov/40258949)

1. Wedan, Riley J.; Longenecker, Jacob Z.; Nowinski, Sara M. (January 2024). "Mitochondrial fatty acid synthesis is an emergent central regulator of mammalian oxidative metabolism". *Cell Metabolism*. **36** (1): 36–47. [doi:10.1016/j.cmet.2023.11.017](https://doi.org/10.1016/j.cmet.2023.11.017). [PMC 10843818](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10843818). [PMID 38128528](https://pubmed.ncbi.nlm.nih.gov/38128528)

1. Heimer G, Kerätär JM, Riley LG, Balasubramaniam S, Eyal E, Pietikäinen LP, Hiltunen JK, Marek-Yagel D, Hamada J, Gregory A, Rogers C, Hogarth P, Nance MA, Shalva N, Veber A, Tzadok M, Nissenkorn A, Tonduti D, Renaldo F, Kraoua I, Panteghini C, Valletta L, Garavaglia B, Cowley MJ, Gayevskiy V, Roscioli T, Silberstein JM, Hoffmann C, Raas-Rothschild A, Tiranti V, Anikster Y, Christodoulou J, Kastaniotis AJ, Ben-Zeev B, Hayflick SJ (December 2016). "MECR Mutations Cause Childhood-Onset Dystonia and Optic Atrophy, a Mitochondrial Fatty Acid Synthesis Disorder". *American Journal of Human Genetics*. **99** (6): 1229–1244. [doi:10.1016/j.ajhg.2016.09.021](https://doi.org/10.1016/j.ajhg.2016.09.021). [PMC 5142118](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5142118). [PMID 27817865](https://pubmed.ncbi.nlm.nih.gov/27817865)

1. Zhang, Shuangxi; Liu, Ruichen; Liu, Quanyu; Liu, Jiankang; Long, Jiangang; Shi, Le (January 2026). "Mitochondrial fatty acid synthesis: The physiopathological role in cellular processes and human diseases". *Genes & Diseases*. [doi:10.1016/j.gendis.2026.102034](https://doi.org/10.1016/j.gendis.2026.102034). [ISSN 2352-3042](https://www.worldcat.org/issn/2352-3042)

1. Jia, Nan; Yu, Shuiqing; Zhang, Geng; Li, Lin; Wang, Jiawei; Lai, Chuntao (April 2024). "Recurrent MECR R258W causes adult-onset optic atrophy: A case report". *European Journal of Medical Genetics*. **68**. [doi:10.1016/j.ejmg.2024.104917](https://doi.org/10.1016/j.ejmg.2024.104917). [ISSN 1769-7212](https://www.worldcat.org/issn/1769-7212)

1. Fiorini, Claudio; Degiorgi, Andrea; Cascavilla, Maria Lucia; Tropeano, Concetta Valentina; La Morgia, Chiara; Battista, Marco; Ormanbekova, Danara; Palombo, Flavia; Carbonelli, Michele; Bandello, Francesco; Carelli, Valerio; Maresca, Alessandra; Barboni, Piero; Baruffini, Enrico; Caporali, Leonardo (January 2024). "Recessive MECR pathogenic variants cause an LHON-like optic neuropathy". *Journal of Medical Genetics*. **61** (1): 93–101. [doi:10.1136/jmg-2023-109340](https://doi.org/10.1136/jmg-2023-109340). [ISSN 0022-2593](https://www.worldcat.org/issn/0022-2593). [PMC 10804020](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10804020). [PMID 37734847](https://pubmed.ncbi.nlm.nih.gov/37734847)

## Further reading

- Torkko JM, Koivuranta KT, Miinalainen IJ, Yagi AI, Schmitz W, Kastaniotis AJ, Airenne TT, Gurvitz A, Hiltunen KJ (September 2001). "Candida tropicalis Etr1p and Saccharomyces cerevisiae Ybr026p (Mrf1'p), 2-enoyl thioester reductases essential for mitochondrial respiratory competence". *Molecular and Cellular Biology*. **21** (18): 6243–53. [doi:10.1128/MCB.21.18.6243-6253.2001](https://doi.org/10.1128/MCB.21.18.6243-6253.2001). [PMC 87346](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC87346). [PMID 11509667](https://pubmed.ncbi.nlm.nih.gov/11509667)
- Maruyama K, Sugano S (January 1994). "Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides". *Gene*. **138** (1–2): 171–4. [doi:10.1016/0378-1119(94)90802-8](https://doi.org/10.1016/0378-1119(94)90802-8). [PMID 8125298](https://pubmed.ncbi.nlm.nih.gov/8125298)
- Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, Suyama A, Sugano S (October 1997). "Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library". *Gene*. **200** (1–2): 149–56. [doi:10.1016/S0378-1119(97)00411-3](https://doi.org/10.1016/S0378-1119(97)00411-3). [PMID 9373149](https://pubmed.ncbi.nlm.nih.gov/9373149)
- Lai CH, Chou CY, Ch'ang LY, Liu CS, Lin W (May 2000). "Identification of novel human genes evolutionarily conserved in Caenorhabditis elegans by comparative proteomics". *Genome Research*. **10** (5): 703–13. [doi:10.1101/gr.10.5.703](https://doi.org/10.1101/gr.10.5.703). [PMC 310876](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC310876). [PMID 10810093](https://pubmed.ncbi.nlm.nih.gov/10810093)

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Adapted from the Wikipedia article [MECR](https://en.wikipedia.org/wiki/MECR) by Wikipedia contributors ([contributor history](https://en.wikipedia.org/wiki/MECR?action=history)). Available under [Creative Commons Attribution-ShareAlike 4.0 International](https://creativecommons.org/licenses/by-sa/4.0/). Changes may have been made.