TbLpn, a key enzyme in lipid droplet formation and phospholipid metabolism, is essential for mitochondrial integrity and growth of Trypanosoma brucei.

Dawoody Nejad, Ladan; Serricchio, Mauro; Jelk, Jennifer; Hemphill, Andrew; Bütikofer, Peter (2018). TbLpn, a key enzyme in lipid droplet formation and phospholipid metabolism, is essential for mitochondrial integrity and growth of Trypanosoma brucei. (In Press). Molecular microbiology Wiley 10.1111/mmi.13976

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Mammalian phosphatidic acid phosphatases, also called lipins, show high amino acid sequence identity to Saccharomyces cerevisiae Pah1p and catalyze the dephosphorylation of phosphatidic acid (PA) to diacylglycerol. Both the substrate and product of the reaction are key precursors for the synthesis of phospholipids and triacylglycerol (TAG). We now show that expression of the Trypanosoma brucei lipin homolog TbLpn is essential for parasite survival in culture. Inducible down-regulation of TbLpn in T. brucei procyclic forms increased cellular PA content, decreased the numbers of lipid droplets, reduced TAG steady-state levels and inhibited in vivo [ H]TAG formation after labeling trypanosomes with [ H]glycerol. In addition, fluorescence and transmission electron microscopy revealed that depletion of TbLpn caused major alterations in mitochondrial morphology and function, i.e., the appearance of distorted mitochondrial matrix, and reduced ATP production via oxidative phosphorylation. Effects of lipin depletion on mitochondrial integrity have previously not been reported. N- and C-terminally tagged forms of TbLpn were localized in the cytosol.

Item Type:

Journal Article (Original Article)

Division/Institute:

05 Veterinary Medicine > Department of Infectious Diseases and Pathobiology (DIP) > Institute of Parasitology
04 Faculty of Medicine > Pre-clinic Human Medicine > Institute of Biochemistry and Molecular Medicine

Graduate School:

Graduate School for Cellular and Biomedical Sciences (GCB)

UniBE Contributor:

Dawoody Nejad, Ladan; Serricchio, Mauro; Jelk, Jennifer; Hemphill, Andrew and Bütikofer, Peter

Subjects:

600 Technology > 630 Agriculture
500 Science > 570 Life sciences; biology
600 Technology > 610 Medicine & health

ISSN:

0950-382X

Publisher:

Wiley

Language:

English

Submitter:

Barbara Järmann-Bangerter

Date Deposited:

27 Feb 2019 16:44

Last Modified:

23 Oct 2019 11:31

Publisher DOI:

10.1111/mmi.13976

PubMed ID:

29679486

BORIS DOI:

10.7892/boris.125025

URI:

https://boris.unibe.ch/id/eprint/125025

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