title: A mitochondrial protein affects cell morphology, mitochondrial segregation and virulence in Leishmania.
abstract: The single mitochondrion of kinetoplastids divides in synchrony with the nucleus and plays a crucial role in cell division. However, despite its importance and potential as a drug target, the mechanism of mitochondrial division and segregation and the molecules involved are only partly understood. In our quest to identify novel mitochondrial proteins in Leishmania, we constructed a hidden Markov model from the targeting motifs of known mitochondrial proteins as a tool to search the Leishmania major genome. We show here that one of the 17 proteins of unknown function that we identified, designated mitochondrial protein X (MIX), is an oligomeric protein probably located in the inner membrane and expressed throughout the Leishmania life cycle. The MIX gene appears to be essential. Moreover, even deletion of one allele from L. major led to abnormalities in cell morphology, mitochondrial segregation and, importantly, to loss of virulence. MIX is unique to kinetoplastids but its heterologous expression in Saccharomyces cerevisiae produced defects in mitochondrial morphology. Our data show that a number of mitochondrial proteins are unique to kinetoplastids and some, like MIX, play a central role in mitochondrial segregation and cell division, as well as virulence.
authors.affiliation: The Walter and Eliza Hall Institute of Medical Research, Vic., Australia.
authors.forename: Alessandro D
authors.initials: AD
authors.lastname: Uboldi
authors.forename: Franziska B
authors.initials: FB
authors.lastname: Lueder
authors.forename: Peter
authors.initials: P
authors.lastname: Walsh
authors.forename: Timothy
authors.initials: T
authors.lastname: Spurck
authors.forename: Geoffrey I
authors.initials: GI
authors.lastname: McFadden
authors.forename: Joan
authors.initials: J
authors.lastname: Curtis
authors.forename: Vladimir A
authors.initials: VA
authors.lastname: Likic
authors.forename: Matthew A
authors.initials: MA
authors.lastname: Perugini
authors.forename: Mary
authors.initials: M
authors.lastname: Barson
authors.forename: Trevor
authors.initials: T
authors.lastname: Lithgow
authors.forename: Emanuela
authors.initials: E
authors.lastname: Handman
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002455:Cell Division / Q000235:genetics; D017353:Gene Deletion; D018503:Genome, Protozoan / Q000235:genetics; D016830:Kinetoplastida / Q000737:chemistry / Q000235:genetics / Q000648:ultrastructure; D018320:Leishmania major / Q000737:chemistry / Q000235:genetics* / Q000648:ultrastructure; D016773:Leishmaniasis, Cutaneous / Q000235:genetics / Q000378:metabolism; D008018:Life Cycle Stages; D008390:Markov Chains; D051379:Mice; D008807:Mice, Inbred BALB C; D008855:Microscopy, Electron, Scanning / Q000379:methods; D008928:Mitochondria / Q000737:chemistry / Q000235:genetics; D051336:Mitochondrial Membranes / Q000737:chemistry; D024101:Mitochondrial Proteins / Q000235:genetics*; D012441:Saccharomyces cerevisiae / Q000737:chemistry / Q000235:genetics; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry / Q000235:genetics; D014345:Trypanosoma / Q000737:chemistry / Q000235:genetics / Q000648:ultrastructure; D014774:Virulence / Q000235:genetics
chemical_list: D024101:Mitochondrial Proteins; D029701:Saccharomyces cerevisiae Proteins