Lipase-like 5 enzyme controls mitochondrial activity in response to starvation in Caenorhabditis elegans
2020
Macedo, Felipe | Martins, Gabriel Loureiro | Luévano-Martínez, Luis A. | Viana, Gustavo Monteiro | Riske, Karin A. | Inague, Alex | Yoshinaga, Marcos Y. | Aguilaniu, Hugo | Miyamoto, Sayuri | Glezer, Isaias | da Cunha, Fernanda Marques
The C. elegans lipase-like 5 (lipl-5) gene is predicted to code for a lipase homologous to the human gastric acid lipase. Its expression was previously shown to be modulated by nutritional or immune cues, but nothing is known about its impact on the lipid landscape and ensuing functional consequences. In the present work, we used mutants lacking LIPL-5 protein and found that lipl-5 is important for normal lipidome composition as well as its remodeling in response to food deprivation. Particularly, lipids with signaling functions such as ceramides and mitochondrial lipids were affected by lipl-5 silencing. In comparison with wild type worms, animals lacking LIPL-5 were enriched in cardiolipins linked to polyunsaturated C20 fatty acids and coenzyme Q-9. Differences in mitochondrial lipid composition were accompanied by differences in mitochondrial activity as mitochondria from well-fed lipl-5 mutants were significantly more able to oxidize respiratory substrates when compared with mitochondria from well-fed wild type worms. Strikingly, starvation elicited important changes in mitochondrial activity in wild type worms, but not in lipl-5 worms. This indicates that this lipase is a determinant of mitochondrial functional remodeling in response to food withdrawal.
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