MMM1 ENCODES A MITOCHONDRIAL OUTER-MEMBRANE PROTEIN ESSENTIAL FOR ESTABLISHING AND MAINTAINING THE STRUCTURE OF YEAST MITOCHONDRIA

In the yeast Saccharomyces cerevisiae, mitochondria are elongated orga nelles which form a reticulum around the eel periphery. To determine t he mechanism by which mitochondrial shape is established and maintaine d, we screened yeast mutants for those defective in mitochondrial morp hology One of these mutants, mmm1, is temperature-sensitive for the ex ternal shape of its mitochondria. At the restrictive temperature, elon gated mitochondria appear to quickly collapse into large, spherical or ganelles. Upon return to the permissive temperature, wild-type mitocho ndrial structure is restored. The morphology of other cellular organel les is not affected in mmm1 mutants, and mmm1 does not disrupt normal actin or tubulin organization. Cells disrupted in the MMM1 gene are in viable when grown on nonfermentable carbon sources and show abnormal m itochondrial morphology at all temperatures. The lethality of mmm1 mut ants appears to result from the inability to segregate the aberrant-sh aped mitochondria into daughter cells. Mitochondrial structure is ther efore important for normal cell function. Mmm1p is located in the mito chondrial outer membrane, with a large carboxyl-terminal domain facing the cytosol. We propose that Mmm1p maintains mitochondria in an elong ated shape by attaching the mitochondrion to an external framework, su ch as the cytoskeleton.