The mdm17 mutation causes temperature-dependent defects in mitochondrial inheritance, mitochondrial morphology, and the maintenance of mitochondrial DNA in the yeast Saccharomyces cerevisiae. Defects in mitochondrial transmission to daughter buds and changes in mitochondrial morphology were apparent within 30 min after shifting cells to 37°C, while loss of the mitochondrial genome occurred after 4–24 h at the elevated temperature. The mdm17 lesion mapped to MGM1, a gene encoding a dynamin-like GTPase previously implicated in mitochondrial genome maintenance, and the cloned MGM1 gene complements all of the mdm17 mutant phenotypes. Cells with an mgm1-null mutation displayed aberrant mitochondrial inheritance and morphology. A version of mgm1 mutated in a conserved residue in the putative GTP-binding site was unable to complement any of the mutant defects. It also caused aberrant mitochondrial distribution and morphology when expressed at high levels in cells that also contained a wild-type copy of the gene. Mgm1p was localized to the mitochondrial outer membrane and fractionated as a component of a high molecular weight complex. These results indicate that Mgm1p is a mitochondrial inheritance and morphology component that functions on the mitochondrial surface.
The Yeast Dynamin-like Protein, Mgm1p, Functions on the Mitochondrial Outer Membrane to Mediate Mitochondrial Inheritance
Address correspondence to Dr. Michael Yaffe, Department of Biology, 0347, University of California, San Diego, La Jolla, CA 92093-0347. Tel.: 619-534-4769. Fax: 619-534-4403. E-mail: [email protected]
This paper is dedicated to the memory of Segall Livneh (1973–1991), who generated the collection of temperature-sensitive strains from which the mdm17 mutant was isolated. We are grateful to Randy Hampton, Karen Berger, and Peter Fekkes for valuable comments on the manuscript and members of the Yaffe lab for their insightful advice and helpful suggestions. We thank Rick Roberts for purification of membrane fractions, Jim Kadonaga for use of the FPLC apparatus, and Alan Kutach for his invaluable help in FPLC analysis.
Kelly A. Shepard, Michael P. Yaffe; The Yeast Dynamin-like Protein, Mgm1p, Functions on the Mitochondrial Outer Membrane to Mediate Mitochondrial Inheritance . J Cell Biol 22 February 1999; 144 (4): 711–720. doi: https://doi.org/10.1083/jcb.144.4.711
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