Characterization and developmentally regulated localization of the mitochondrial carrier protein homologue MCP6 from Trypanosoma brucei.
Proteins of the mitochondrial carrier family (MCF) are located mainly in the inner mitochondrial membrane and mediate the transport of a large range of metabolic intermediates. The genome of Trypanosoma brucei harbors 29 genes encoding different MCF proteins. We describe here the characterization of MCP6, a novel T. brucei MCF protein. Sequence comparison and phylogenetic reconstruction revealed that MCP6 is closely related to different mitochondrial ADP/ATP and calcium-dependent solute carriers, including the ATP-Mg/Pi carrier of Homo sapiens. However, MCP6 lacks essential amino acids and sequence motifs conserved in these metabolite transporters, and functional reconstitution and transport assays with E. coli suggested that this protein indeed does not function as an ADP/ATP or ATP-Mg/Pi carrier. The subcellular localization of MCP6 is developmentally regulated: in bloodstream-form trypanosomes, the protein is predominantly glycosomal, whereas in the procyclic form, it is found mainly in the mitochondria. Depletion of MCP6 in procyclic trypanosomes resulted in growth inhibition, an increased cell size, aberrant numbers of nuclei and kinetoplasts, and abnormal kinetoplast morphology, suggesting that depletion of MCP6 inhibits division of the kinetoplast.
Colasante
Claudia
C
Zentrum für Molekulare Biologie (ZMBH), Im Neuenheimer Feld 282, D-69120 Heidelberg, Germany.
Alibu
Vincent P
VP
Kirchberger
Simon
S
Tjaden
Joachim
J
Clayton
Christine
C
Voncken
Frank
F
D000818:Animals; D001483:Base Sequence; D004926:Escherichia coli / Q000235:genetics; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D051336:Mitochondrial Membranes / Q000737:chemistry*; D024101:Mitochondrial Proteins / Q000737:chemistry* / Q000235:genetics*; D008969:Molecular Sequence Data; D010802:Phylogeny; D015800:Protozoan Proteins / Q000737:chemistry* / Q000235:genetics*; D012333:RNA, Messenger / Q000096:biosynthesis; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D014346:Trypanosoma brucei brucei / Q000235:genetics* / Q000254:growth & development
D024101:Mitochondrial Proteins; D015800:Protozoan Proteins; D012333:RNA, Messenger