MECR

MECR
Identifiers
AliasesMECR, CGI-63, FASN2B, NRBF1, mitochondrial trans-2-enoyl-CoA reductase, ETR1, nuclear receptor binding factor 1, trans-2-enoyl-CoA reductase, mitochondrial, mitochondrial 2-enoyl thioester reductase
External IDsOMIM: 608205; MGI: 1349441; GeneCards: MECR
Available structures
PDBOrtholog search: PDBe RCSB
Enzyme activity
EC #BRENDAExPASyKEGGMetaCyc
1.3.1.104↗↗↗↗
Orthologs
DatabasesNCBI: entry; OMA: entry
SpeciesHumanMouse
Entrez

51102

26922

Ensembl

ENSG00000116353

ENSMUSG00000028910

UniProt

Q9BV79

Q9DCS3

RefSeq (mRNA)

NM_025297

RefSeq (protein)

NP_079573

Location (UCSC)Chr 1: 29.19 – 29.23 MbChr 4: 131.57 – 131.6 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Mitochondrial trans-2-enoyl-CoA reductase (MECR) is an enzyme that in humans is encoded by the MECR gene.[5] It belongs to the enzyme class of oxidoreductases and catalyzes the last step of mitochondrial fatty acid synthesis (mtFAS).[6] In doing so, MECR makes the fatty acyl chain bound to mitochondrial acyl carrier protein (mtACP) available again for elongation.[7] MECR thereby contributes to mitochondrial respiration and oxidative phosphorylation.[8] Beyond its mitochondrial role, a cytosolic and nuclear isoform (cMECR) has been linked to PPARα-dependent transcription.[9] Pathogenic variants in the MECR gene cause MEPAN syndrome.[8]

Structure

The MECR gene is located on chromosome 1 at locus p35.3 and contains 18 exons.[6] Through alternative splicing, it produces nine protein-coding mRNA transcripts, which encode five isoforms of mitochondrial trans-2-enoyl-CoA reductase (MECR).[6] The cMECR isoform lacks the N-terminal mitochondrial targeting sequence and localizes to the cytosol and nucleus.[9]

MECR forms a dimer with a bent substrate-binding cavity between the two monomers that accommodates acyl substrates with carbon chain lengths from C4 to C16.[10][11]

Reaction

The reaction catalyzed by MECR can be summarized as follows:

trans-2-enoyl-mtACP + NADPH + H+ → acyl-mtACP + NADP+

Function

MECR catalyzes the last step of the mitochondrial fatty acid synthesis pathway. By using NADPH to reduce trans-2-enoyl-mtACP to saturated acyl-mtACP, MECR prepares the acyl chain for another round of elongation.

The MECR gene encodes mitochondrial trans-2-enoyl-CoA reductase, which catalyzes the last step of mitochondrial fatty acid synthesis (mtFAS).[8] Condensation in mtFAS produces an unsaturated fatty acyl chain bound to mtACP.[7] It must undergo reduction and dehydration reactions to become saturated, making it available again for the next elongation cycle.[7] MECR completes this process by reducing the trans double bond between carbon atoms 2 and 3, yielding a saturated acyl-mtACP species.[12] NADPH, whose availability in mitochondria depends on NADK2, provides the required reducing power.[13] Through repeated elongation cycles, mitochondrial fatty acid synthesis generates acyl-mtACP species with chain lengths from C2 to C16.[14] Octanoyl-mtACP (C8) serves as the precursor for lipoic acid biosynthesis and subsequent protein lipoylation, which is essential for several mitochondrial enzyme complexes, including the pyruvate dehydrogenase complex, the 2-oxoglutarate dehydrogenase complex, the branched-chain alpha-keto acid dehydrogenase complex, the 2-oxoadipate dehydrogenase complex, and the glycine cleavage system.[15] Longer-chain acyl-mtACP species interact with LYRM proteins that are required for iron–sulfur cluster biogenesis and respiratory-chain assembly.[15] In addition, mtFAS has been linked to mitochondrial translation and to levels of polyamines, including spermidine and spermine, as well as bioactive lipids such as lysophospholipids and sphingolipids.[13][10]

MECR has also been reported to bind transcription factors of the PPAR family and activate transcription, suggesting a possible link between nuclear gene regulation and mtFAS.[8]

Clinical significance

Pathogenic variants in the MECR gene cause MEPAN syndrome, a rare autosomal recessive mitochondrial metabolic disorder characterized by childhood-onset dystonia, optic atrophy, and basal ganglia signal abnormalities on MRI.[16] A later-onset phenotype with LHON-like optic neuropathy but without movement disorder or basal ganglia signal abnormalities has also been reported.[17][18][19]

See also

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000116353 – Ensembl, May 2017
  2. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000028910 – Ensembl, May 2017
  3. ↑ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ↑ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ↑ "Gene symbol report | HUGO Gene Nomenclature Committee". www.genenames.org. Retrieved 2026-05-19.
  6. 1 2 3 "MECR mitochondrial trans-2-enoyl-CoA reductase [Homo sapiens (human)] - Gene - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2026-05-19.
  7. 1 2 3 Nowinski SM, Solmonson A, Rusin SF, et al. (2020-08-17). "Mitochondrial fatty acid synthesis coordinates oxidative metabolism in mammalian mitochondria". eLife. 9. doi:10.7554/eLife.58041. ISSN 2050-084X. PMC 7470841. PMID 32804083.
  8. 1 2 3 4 Murdock DG, Janssen KA, Keller K, et al. (2025-10-07). "A mouse model of MEPAN demonstrates a role for mitochondrial fatty acid synthesis in iron–sulfur cluster and supercomplex formation". Proceedings of the National Academy of Sciences. 122 (40). doi:10.1073/pnas.2506761122. ISSN 0027-8424. PMC 12519216. PMID 41021813.
  9. 1 2 Kim DG, Yoo JC, Kim E, et al. (2014). "A Novel Cytosolic Isoform of Mitochondrial Trans-2-Enoyl-CoA Reductase Enhances Peroxisome Proliferator-Activated Receptor α Activity". Endocrinology and Metabolism. 29 (2): 185. doi:10.3803/EnM.2014.29.2.185. ISSN 2093-596X. PMC 4091492. PMID 25031892.
  10. 1 2 Clay HB, Parl AK, Mitchell SL, et al. (2016-03-10). Peterson J (ed.). "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) e0151171. doi:10.1371/journal.pone.0151171. ISSN 1932-6203. PMC 4786287. PMID 26963735.
  11. ↑ Rahman MT, Koski MK, Panecka-Hofman J, et al. (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. ISSN 2041-1723. PMC 9899272. PMID 36739436.
  12. ↑ Wedan RJ, Longenecker JZ, Nowinski SM (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. PMC 10843818. PMID 38128528.
  13. 1 2 Wedan RJ, Nowinski SM (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. PMC 12507123. PMID 40680726.
  14. ↑ Kim D, Kesavan R, Ryu K, et al. (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. ISSN 1465-7392. PMC 12331256. PMID 40258949.
  15. 1 2 Wedan RJ, Longenecker JZ, Nowinski SM (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. PMC 10843818. PMID 38128528.
  16. ↑ Heimer G, Kerätär JM, Riley LG, et al. (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. PMC 5142118. PMID 27817865.
  17. ↑ Zhang S, Liu R, Liu Q, et al. (January 2026). "Mitochondrial fatty acid synthesis: The physiopathological role in cellular processes and human diseases". Genes & Diseases 102034. doi:10.1016/j.gendis.2026.102034. ISSN 2352-3042.
  18. ↑ Jia N, Yu S, Zhang G, et al. (April 2024). "Recurrent MECR R258W causes adult-onset optic atrophy: A case report". European Journal of Medical Genetics. 68 104917. doi:10.1016/j.ejmg.2024.104917. ISSN 1769-7212.
  19. ↑ Fiorini C, Degiorgi A, Cascavilla ML, et al. (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. ISSN 0022-2593. PMC 10804020. PMID 37734847.

Further reading

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