Redox-dependent lipoylation of mitochondrial proteins in Plasmodium falciparum

Gustavo A. Afanador, Krista A. Matthews, David Bartee, Jolyn E. Gisselberg, Maroya S. Walters, Caren L. Freel Meyers, Sean T. Prigge

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Lipoate scavenging from the human host is essential for malaria parasite survival. Scavenged lipoate is covalently attached to three parasite proteins: the H-protein and the E2 subunits of branched chain amino acid dehydrogenase (BCDH) and α-ketoglutarate dehydrogenase (KDH). We show mitochondrial localization for the E2 subunits of BCDH and KDH, similar to previously localized H-protein, demonstrating that all three lipoylated proteins reside in the parasite mitochondrion. The lipoate ligase 1, LipL1, has been shown to reside in the mitochondrion and it catalyses the lipoylation of the H-protein; however, we show that LipL1 alone cannot lipoylate BCDH or KDH. A second mitochondrial protein with homology to lipoate ligases, LipL2, does not show ligase activity and is not capable of lipoylating any of the mitochondrial substrates. Instead, BCDH and KDH are lipoylated through a novel mechanism requiring both LipL1 and LipL2. This mechanism is sensitive to redox conditions where BCDH and KDH are exclusively lipoylated under strong reducing conditions in contrast to the H-protein which is preferentially lipoylated under less reducing conditions. Thus, malaria parasites contain two different routes of mitochondrial lipoylation, an arrangement that has not been described for any other organism.

Original languageEnglish (US)
Pages (from-to)156-171
Number of pages16
JournalMolecular Microbiology
Volume94
Issue number1
DOIs
StatePublished - Oct 1 2014

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Lipoylation
Mitochondrial Proteins
Plasmodium falciparum
Oxidation-Reduction
Oxidoreductases
Branched Chain Amino Acids
Parasites
Ligases
Proteins
Malaria
Mitochondria
Protein Subunits

ASJC Scopus subject areas

  • Microbiology
  • Molecular Biology

Cite this

Afanador, G. A., Matthews, K. A., Bartee, D., Gisselberg, J. E., Walters, M. S., Freel Meyers, C. L., & Prigge, S. T. (2014). Redox-dependent lipoylation of mitochondrial proteins in Plasmodium falciparum. Molecular Microbiology, 94(1), 156-171. https://doi.org/10.1111/mmi.12753

Redox-dependent lipoylation of mitochondrial proteins in Plasmodium falciparum. / Afanador, Gustavo A.; Matthews, Krista A.; Bartee, David; Gisselberg, Jolyn E.; Walters, Maroya S.; Freel Meyers, Caren L.; Prigge, Sean T.

In: Molecular Microbiology, Vol. 94, No. 1, 01.10.2014, p. 156-171.

Research output: Contribution to journalArticle

Afanador, GA, Matthews, KA, Bartee, D, Gisselberg, JE, Walters, MS, Freel Meyers, CL & Prigge, ST 2014, 'Redox-dependent lipoylation of mitochondrial proteins in Plasmodium falciparum', Molecular Microbiology, vol. 94, no. 1, pp. 156-171. https://doi.org/10.1111/mmi.12753
Afanador GA, Matthews KA, Bartee D, Gisselberg JE, Walters MS, Freel Meyers CL et al. Redox-dependent lipoylation of mitochondrial proteins in Plasmodium falciparum. Molecular Microbiology. 2014 Oct 1;94(1):156-171. https://doi.org/10.1111/mmi.12753
Afanador, Gustavo A. ; Matthews, Krista A. ; Bartee, David ; Gisselberg, Jolyn E. ; Walters, Maroya S. ; Freel Meyers, Caren L. ; Prigge, Sean T. / Redox-dependent lipoylation of mitochondrial proteins in Plasmodium falciparum. In: Molecular Microbiology. 2014 ; Vol. 94, No. 1. pp. 156-171.
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