Suppression of the ELO-2 FA elongation activity results in alterations of the fatty acid composition and multiple physiological defects, including abnormal ultradian rhythms, in Caenorhabditis elegans.
While the general steps of fatty acid (FA) biosynthesis are well understood, the individual enzymes involved in the elongation of long chain saturated and polyunsaturated FA (PUFA) are largely unknown. Recent research indicates that these enzymes might be of considerable physiological importance for human health. We use Caenorhabditis elegans to study FA elongation activities and associated abnormal phenotypes. In this article we report that the predicted C. elegans F11E6.5/ELO-2 is a functional enzyme with the FA elongation activity. It is responsible for the elongation of palmitic acid and is involved in PUFA biosynthesis. RNAi-mediated suppression of ELO-2 causes an accumulation of palmitate and an associated decrease in the PUFA fraction in triacylglycerides and phospholipid classes. This imbalance in the FA composition results in multiple phenotypic defects such as slow growth, small body size, reproductive defects, and changes in rhythmic behavior. ELO-2 cooperates with the previously reported ELO-1 in 20-carbon PUFA production, and at least one of the enzymes must function to provide normal growth and development in C. elegans. The presented data indicate that suppression of a single enzyme of the FA elongation machinery is enough to affect various organs and systems in worms. This effect resembles syndromic disorders in humans.
Kniazeva
Marina
M
Howard Hughes Medical Institute and Department of Molecular, Cellular, and Developmental Biology, University of Colorado, Boulder, Colorado 80309, USA. marinak@colorado.edu
Sieber
Matt
M
McCauley
Scott
S
Zhang
Kang
K
Watts
Jennifer L
JL
Han
Min
M
D000123:Acetyltransferases / Q000235:genetics / Q000378:metabolism*; D000204:Activity Cycles / Q000235:genetics / Q000502:physiology*; D000595:Amino Acid Sequence; D000818:Animals; D017173:Caenorhabditis elegans / Q000201:enzymology / Q000235:genetics / Q000378:metabolism*; D000081031:Fatty Acid Elongases; D005227:Fatty Acids / Q000096:biosynthesis*; D008969:Molecular Sequence Data; D005810:Multigene Family; D019308:Palmitic Acid / Q000378:metabolism; D034622:RNA Interference
D005227:Fatty Acids; D019308:Palmitic Acid; D000123:Acetyltransferases; D000081031:Fatty Acid Elongases