ArticleNature communications2023
An engineered variant of MECR reductase reveals indispensability of long-chain acyl-ACPs for mitochondrial respiration.
Article in Nature communications, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed, 17 citations in OpenAlex.
- Functional partitioning of lipoic acid decouples cellular abundance from mitochondrial utilization.bioRxiv : the preprint server for biology · 2026Article
- Integrative Transcriptomic Analysis Identifies Novel Mitochondrial Gene Targets in Parkinson's Disease.Molecular neurobiology · 2026Article
- The mitochondrial trans-2-enoyl-CoA reductase is necessary for mitochondrial homeostasis in C. elegans.Genetics · 2025Article
- 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 of the United States of America · 2025Article
- Mitochondrial NADPH fuels mitochondrial fatty acid synthesis and lipoylation to power oxidative metabolism.Nature cell biology · 2025Article
- Mitochondrial fatty acid synthesis and MECR regulate CD4+ T cell function and oxidative metabolism.Journal of immunology (Baltimore, Md. : 1950) · 2025Article
- Fatty acid metabolism related gene MECR contributes to the progression of prostate cancer.Cancer cell international · 2025Article
- Mitochondrial fatty acid synthesis is an emergent central regulator of mammalian oxidative metabolism.Cell metabolism · 2024Review
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Authors and funding
9 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Mitochondrial fatty acid synthesis (mtFAS) is essential for respiratory function. MtFAS generates the octanoic acid precursor for lipoic acid synthesis, but the role of longer fatty acid products has remained unclear. The structurally well-characterized component of mtFAS, human 2E-enoyl-ACP reductase (MECR) rescues respiratory growth and lipoylation defects of a Saccharomyces cerevisiae Δetr1 strain lacking native mtFAS enoyl reductase. To address the role of longer products of mtFAS, we employed in silico molecular simulations to design a MECR variant with a shortened substrate binding cavity. Our in vitro and in vivo analyses indicate that the MECR G165Q variant allows synthesis of octanoyl groups but not long chain fatty acids, confirming the validity of our computational approach to engineer substrate length specificity. Furthermore, our data imply that restoring lipoylation in mtFAS deficient yeast strains is not sufficient to support respiration and that long chain acyl-ACPs generated by mtFAS are required for mitochondrial function.
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Registered trials
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