Fatty acid oxidation is essential for egg production by the parasitic flatworm Schistosoma mansoni.
Fatty acid oxidation is essential for egg production by the parasitic flatworm Schistosoma mansoni.
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DOI：
10.1371/journal.ppat.1002996
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发表时间：
2012
期刊：
影响因子：
6.7
通讯作者：
Pearce EJ
中科院分区：
文献类型：
--
作者：
Huang SC;Freitas TC;Amiel E;Everts B;Pearce EL;Lok JB;Pearce EJ
Schistosomes, parasitic flatworms that cause the neglected tropical disease schistosomiasis, have been considered to have an entirely carbohydrate based metabolism, with glycolysis playing a dominant role in the adult parasites. However, we have discovered a close link between mitochondrial oxygen consumption by female schistosomes and their ability to produce eggs. We show that oxygen consumption rates (OCR) and egg production are significantly diminished by pharmacologic inhibition of carnitine palmitoyl transferase 1 (CPT1), which catalyzes a rate limiting step in fatty acid β-oxidation (FAO) and by genetic loss of function of acyl CoA synthetase, which complexes with CPT1 and activates long chain FA for use in FAO, and of acyl CoA dehydrogenase, which catalyzes the first step in FAO within mitochondria. Declines in OCR and egg production correlate with changes in a network of lipid droplets within cells in a specialized reproductive organ, the vitellarium. Our data point to the importance of regulated lipid stores and FAO for the compartmentalized process of egg production in schistosomes. Schistosomes are parasitic worms that are the cause of the Neglected Tropical Disease schistosomiasis. Female schistosomes mated with males produce eggs, which either pass out of the host's body for transmission of the infection, or become trapped in host tissues, where they induce inflammation that contributes to disease symptoms. It has been assumed that egg production is a bioenergetically-demanding process fuelled by glucose metabolism. However, we have discovered that egg production is blocked by inhibition of fatty acid oxidation (FAO), the process through which FA are utilized within mitochondria to fuel the tricarboxylic acid cycle and thereby produce substrates for ATP synthesis through oxidative phosphorylation. Consistent with a role for FAO in egg production, fecund females have extensive fat stores, in the form of lipid droplets, whereas virgin adult females have little or no fat reserves. Moreover, fecund females placed into tissue culture exhaust their fat reserves and cease to be able to produce eggs. Since schistosomes cannot produce their own FA, our data point to the acquisition of FA from the host as a key process necessary for egg production. Our findings point to the importance of regulated lipid stores and FAO for egg production by schistosomes.
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影响因子：
2.4
作者：
Mann VH;Morales ME;Rinaldi G;Brindley PJ
通讯作者：
Brindley PJ
影响因子：
--
作者：
Balog, Crina I. A.;Meissner, Axel;Deelder, Andre M.
通讯作者：
Deelder, Andre M.
影响因子：
2.4
作者：
ERASMUS, DA;POPIEL, I;SHAW, JR
通讯作者：
SHAW, JR
影响因子：
4.8
作者：
Kim, JH;Lewin, TM;Coleman, RA
通讯作者：
Coleman, RA
影响因子：
4
作者：
Guo, Yi;Cordes, Kimberly R.;Walther, Tobias C.
通讯作者：
Walther, Tobias C.