MMI1 (YKL056c, TMA19), the yeast orthologue of the translationally controlled tumor protein (TCTP) has apoptotic functions and interacts with both microtubules and mitochondria.
The yeast orthologue of mammalian TCTP is here proposed to be named Mmi1p (microtubule and mitochondria interacting protein). This protein displays about 50% amino acid sequence identity with its most distantly related orthologs in higher organisms and therefore probably belongs to a small class of yeast proteins which have housekeeping but so far incompletely known functions needed for every eukaryotic cell. Previous investigations of the protein in both higher cells and yeast revealed that it is highly expressed during active growth, but transcriptionally down-regulated in several kinds of stress situations including starvation stress. In human cells, TCTP presumably has anti-apoptotic functions as it binds to Bcl-XL in vivo. TCTP of higher cells was also shown to interact with the translational machinery. It has acquired an additional function in the mammalian immune system, as it is identical with the histamine releasing factor. Here, we show that in S. cerevisiae induction of apoptosis by mild oxidative stress, replicative ageing or mutation of cdc48 leads to translocation of Mmi1p from the cytoplasm to the mitochondria. Mmi1p is stably but reversibly attached to the outer surface of the mitochondria and can be removed by digestion with proteinase K. Glutathionylation of Mmi1p, which is also induced by oxidants, is not a prerequisite or signal for translocation as shown by replacing the only cysteine of Mmi1p by serine. Mmi1p probably interacts with yeast microtubules as deletion of the gene confers sensitivity to benomyl. Conversely, the deletion mutant displays resistance to hydrogen peroxide stress and shows a small but significant elongation of the mother cell-specific lifespan. Our results so far indicate that Mmi1p is one of the few proteins establishing a functional link between microtubules and mitochondria which may be needed for correct localization of mitochondria during cell division.
Rinnerthaler
Mark
M
Department of Cell Biology, Division of Genetics, University of Salzburg, Austria.
Jarolim
Stefanie
S
Heeren
Gino
G
Palle
Elfriede
E
Perju
Simona
S
Klinger
Harald
H
Bogengruber
Edith
E
Madeo
Frank
F
Braun
Ralf J
RJ
Breitenbach-Koller
Lore
L
Breitenbach
Michael
M
Laun
Peter
P
D000251:Adenosine Triphosphatases; D000595:Amino Acid Sequence; D017209:Apoptosis; D014408:Biomarkers, Tumor; D002135:Calcium-Binding Proteins; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D003593:Cytoplasm / Q000502:physiology; D006801:Humans; D066298:In Vitro Techniques; D008870:Microtubules / Q000502:physiology*; D008928:Mitochondria / Q000502:physiology*; D008969:Molecular Sequence Data; D009154:Mutation; D009363:Neoplasm Proteins / Q000235:genetics; D009687:Nuclear Proteins / Q000235:genetics; D018384:Oxidative Stress; D010766:Phosphorylation; D021381:Protein Transport; D012441:Saccharomyces cerevisiae / Q000502:physiology*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000502:physiology*; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction; D000090324:Tumor Protein, Translationally-Controlled 1; D000074405:Valosin Containing Protein
D014408:Biomarkers, Tumor; D002135:Calcium-Binding Proteins; D018797:Cell Cycle Proteins; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D029701:Saccharomyces cerevisiae Proteins; C513776:TMA19 protein, S cerevisiae; C000715647:TPT1 protein, human; D000090324:Tumor Protein, Translationally-Controlled 1; D000251:Adenosine Triphosphatases; C000614177:CDC48 protein, S cerevisiae; D000074405:Valosin Containing Protein