ArticleThe Journal of biological chemistry2009
Down-regulation of mitochondrial acyl carrier protein in mammalian cells compromises protein lipoylation and respiratory complex I and results in cell death.
Article in The Journal of biological chemistry, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 63 papers.
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Who cites it
63 citing papers in PubMed, 115 citations in OpenAlex.
- Oxidative Phosphorylation System in Gastric Carcinomas and Gastritis.Oxidative medicine and cellular longevity · 2017Trial
- Copper Metabolism-Related Cell Death in Kidney Diseases: Molecular Mechanisms, Disease-Specific Evidence, and Translational Implications.International journal of molecular sciences · 2026Review
- Functional partitioning of lipoic acid decouples cellular abundance from mitochondrial utilization.bioRxiv : the preprint server for biology · 2026Article
- Targeting multiple genetic defects of mitochondrial diseases with a single bacterial lipoate protein ligase.Science advances · 2025Article
- 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
- Alpha-lipoic acid supplementation improves pathological alterations in cellular models of Friedreich ataxia.Orphanet journal of rare diseases · 2025Article
- Identification of DownregulatedInternational journal of molecular sciences · 2025Article
- Defining the necessity of the lipoic acid synthasemicroPublication biology · 2025Article
- A Multi-Target Pharmacological Correction of a LipoyltransferaseAntioxidants (Basel, Switzerland) · 2024Article
- Mitochondrial fatty acid synthesis is an emergent central regulator of mammalian oxidative metabolism.Cell metabolism · 2024Review
- RecessiveJournal of medical genetics · 2023Article
- Substrate Sequestration and Chain Flipping in Human Mitochondrial Acyl Carrier Protein.Biochemistry · 2023Article
- Alpha-lipoic acid supplementation corrects pathological alterations in cellular models of pantothenate kinase-associated neurodegeneration with residual PANK2 expression levels.Orphanet journal of rare diseases · 2023Article
- Weighted Gene Co-Expression Network Analysis (WGCNA) Discovered Novel Long Non-Coding RNAs for Polycystic Ovary Syndrome.Biomedicines · 2023Article
- Pan-cancer patterns of cuproptosis markers reveal biologically and clinically relevant cancer subtypes.Biomarker research · 2023Article
- Alternative splicing liberates a cryptic cytoplasmic isoform of mitochondrial MECR that antagonizes influenza virus.PLoS biology · 2022Article
- Conformational changes in mitochondrial complex I of the thermophilic eukaryoteScience advances · 2022Article
- Therapeutic approach with commercial supplements for pantothenate kinase-associated neurodegeneration with residual PANK2 expression levels.Orphanet journal of rare diseases · 2022Article
- Transcriptome comparative analysis of ovarian follicles reveals the key genes and signaling pathways implicated in hen egg production.BMC genomics · 2021Article
3 more citing papers are in PubMed but not listed here.
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Authors and funding
3 authors.
Funding
Abstract
The objective of this study was to evaluate the physiological importance of the mitochondrial fatty acid synthesis pathway in mammalian cells using the RNA interference strategy. Transfection of HEK293T cells with small interfering RNAs targeting the acyl carrier protein (ACP) component reduced ACP mRNA and protein levels by >85% within 24 h. The earliest phenotypic changes observed were a marked decrease in the proportion of post-translationally lipoylated mitochondrial proteins recognized by anti-lipoate antibodies and a reduction in their catalytic activity, and a slowing of the cell growth rate. Later effects observed included a reduction in the specific activity of respiratory complex I, lowered mitochondrial membrane potential, the development of cytoplasmic membrane blebs containing high levels of reactive oxygen species and ultimately, cell death. Supplementation of the culture medium with lipoic acid offered some protection against oxidative damage but did not reverse the protein lipoylation defect. These observations are consistent with a dual role for ACP in mammalian mitochondrial function. First, as a key component of the mitochondrial fatty acid biosynthetic pathway, ACP plays an essential role in providing the octanoyl-ACP precursor required for the protein lipoylation pathway. Second, as one of the subunits of complex I, ACP is required for the efficient functioning of the electron transport chain and maintenance of normal mitochondrial membrane potential.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.