Monomethyl branched-chain fatty acids play an essential role in Caenorhabditis elegans development

Marina Kniazeva, Quinn T. Crawford, Matt Seiber, Cun Yu Wang, Min Han

Research output: Contribution to journalArticle

114 Citations (Scopus)

Abstract

Monomethyl branched-chain fatty acids (mmBCFAs) are commonly found in many organisms from bacteria to mammals. In humans, they have been detected in skin, brain, blood, and cancer cells. Despite a broad distribution, mmBCFAs remain exotic in eukaryotes, where their origin and physiological roles are not understood. Here we report our study of the function and regulation of mmBCFAs in Caenorhabditis elegans, combining genetics, gas chromatography, and DNA microarray analysis. We show that C. elegans synthesizes mmBCFAs de novo and utilizes the long-chain fatty acid elongation enzymes ELO-5 and ELO-6 to produce two mmBCFAs, C15ISO and C17ISO. These mmBCFAs are essential for C. elegans growth and development, as suppression of their biosynthesis results in a growth arrest at the first larval stage. The arrest is reversible and can be overcome by feeding the arrested animals with mmBCFA supplements. We show not only that the levels of C15ISO and C17ISO affect the expression of several genes, but also that the activities of some of these genes affect biosynthesis of mmBCFAs, suggesting a potential feedback regulation. One of the genes, lpd-1, encodes a homolog of a mammalian sterol regulatory element-binding protein (SREBP 1c). We present results suggesting that elo-5 and elo-6 may be transcriptional targets of LPD-1. This study exposes unexpected and crucial physiological functions of C15ISO and C17ISO in C. elegans and suggests a potentially important role for mmBCFAs in other eukaryotes.

Original languageEnglish (US)
JournalPLoS Biology
Volume2
Issue number9
DOIs
StatePublished - Sep 1 2004

Fingerprint

branched chain fatty acids
Essential Fatty Acids
Caenorhabditis elegans
Fatty Acids
Sterol Regulatory Element Binding Protein 1
Genes
Biosynthesis
Eukaryota
eukaryotic cells
Sterol Regulatory Element Binding Proteins
biosynthesis
Mammals
Microarray Analysis
Microarrays
Oligonucleotide Array Sequence Analysis
animal feeding
Growth and Development
long chain fatty acids
Brain Neoplasms
Gas chromatography

ASJC Scopus subject areas

  • Neuroscience(all)
  • Immunology and Microbiology(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Monomethyl branched-chain fatty acids play an essential role in Caenorhabditis elegans development. / Kniazeva, Marina; Crawford, Quinn T.; Seiber, Matt; Wang, Cun Yu; Han, Min.

In: PLoS Biology, Vol. 2, No. 9, 01.09.2004.

Research output: Contribution to journalArticle

Kniazeva, Marina ; Crawford, Quinn T. ; Seiber, Matt ; Wang, Cun Yu ; Han, Min. / Monomethyl branched-chain fatty acids play an essential role in Caenorhabditis elegans development. In: PLoS Biology. 2004 ; Vol. 2, No. 9.
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