The inner membrane protein Mdm33 controls mitochondrial morphology in yeast.
Mitochondrial distribution and morphology depend on MDM33, a Saccharomyces cerevisiae gene encoding a novel protein of the mitochondrial inner membrane. Cells lacking Mdm33 contain ring-shaped, mostly interconnected mitochondria, which are able to form large hollow spheres. On the ultrastructural level, these aberrant organelles display extremely elongated stretches of outer and inner membranes enclosing a very narrow matrix space. Dilated parts of Delta mdm33 mitochondria contain well-developed cristae. Overexpression of Mdm33 leads to growth arrest, aggregation of mitochondria, and generation of aberrant inner membrane structures, including septa, inner membrane fragments, and loss of inner membrane cristae. The MDM33 gene is required for the formation of net-like mitochondria in mutants lacking components of the outer membrane fission machinery, and mitochondrial fusion is required for the formation of extended ring-like mitochondria in cells lacking the MDM33 gene. The Mdm33 protein assembles into an oligomeric complex in the inner membrane where it performs homotypic protein-protein interactions. Our results indicate that Mdm33 plays a distinct role in the mitochondrial inner membrane to control mitochondrial morphology. We propose that Mdm33 is involved in fission of the mitochondrial inner membrane.
Messerschmitt
Marlies
M
Institut für Physiologische Chemie, Universität München, D-81377 München, Germany.
Jakobs
Stefan
S
Vogel
Frank
F
Fritz
Stefan
S
Dimmer
Kai Stefan
KS
Neupert
Walter
W
Westermann
Benedikt
B
D000595:Amino Acid Sequence; D002176:Candida albicans / Q000235:genetics; D020558:GTP Phosphohydrolases / Q000378:metabolism; D005800:Genes, Fungal; D007425:Intracellular Membranes / Q000378:metabolism; D008164:Luminescent Proteins / Q000378:metabolism; D046911:Macromolecular Substances; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D008928:Mitochondria / Q000378:metabolism* / Q000648:ultrastructure; D024101:Mitochondrial Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D008970:Molecular Weight; D011487:Protein Conformation; D012441:Saccharomyces cerevisiae / Q000166:cytology / Q000235:genetics / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D016415:Sequence Alignment
D008164:Luminescent Proteins; D046911:Macromolecular Substances; D008565:Membrane Proteins; D024101:Mitochondrial Proteins; D029701:Saccharomyces cerevisiae Proteins; C472768:mdm33 protein, S cerevisiae; C401395:FZO1 protein, S cerevisiae; D020558:GTP Phosphohydrolases