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Redox‐dependent lipoylation of mitochondrial proteins in P lasmodium falciparum
Author(s) -
Afanador Gustavo A.,
Matthews Krista A.,
Bartee David,
Gisselberg Jolyn E.,
Walters Maroya S.,
Freel Meyers Caren L.,
Prigge Sean T.
Publication year - 2014
Publication title -
molecular microbiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.857
H-Index - 247
eISSN - 1365-2958
pISSN - 0950-382X
DOI - 10.1111/mmi.12753
Subject(s) - biology , biochemistry , mitochondrion , dna ligase , plasmodium falciparum , microbiology and biotechnology , enzyme , malaria , immunology
Summary 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 E 2 subunits of branched chain amino acid dehydrogenase ( BCDH ) and α‐ketoglutarate dehydrogenase ( KDH ). We show mitochondrial localization for the E 2 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.