A mitochondrial protein affects cell morphology, mitochondrial segregation and virulence in Leishmania.
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.
Uboldi
Alessandro D
AD
The Walter and Eliza Hall Institute of Medical Research, Vic., Australia.
Lueder
Franziska B
FB
Walsh
Peter
P
Spurck
Timothy
T
McFadden
Geoffrey I
GI
Curtis
Joan
J
Likic
Vladimir A
VA
Perugini
Matthew A
MA
Barson
Mary
M
Lithgow
Trevor
T
Handman
Emanuela
E
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
D024101:Mitochondrial Proteins; D029701:Saccharomyces cerevisiae Proteins