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Dnm1p GTPase-mediated mitochondrial fission is a multi-step process requiring the novel integral membrane component Fis1p.

Mozdy AD, McCaffery JM, Shaw JM - J. Cell Biol. (2000)

Bottom Line: Nunnari. 2000.Genetic and morphological evidence indicate that Fis1p, but not Mdv1p, function is required for the proper assembly and distribution of Dnm1p-containing fission complexes on mitochondrial tubules.We propose that mitochondrial fission in yeast is a multi-step process, and that membrane-bound Fis1p is required for the proper assembly, membrane distribution, and function of Dnm1p-containing complexes during fission.

View Article: PubMed Central - PubMed

Affiliation: Department of Biology, University of Utah, Salt Lake City, Utah 84112, USA.

ABSTRACT
Yeast Dnm1p is a soluble, dynamin-related GTPase that assembles on the outer mitochondrial membrane at sites where organelle division occurs. Although these Dnm1p-containing complexes are thought to trigger constriction and fission, little is known about their composition and assembly, and molecules required for their membrane recruitment have not been isolated. Using a genetic approach, we identified two new genes in the fission pathway, FIS1 and FIS2. FIS1 encodes a novel, outer mitochondrial membrane protein with its amino terminus exposed to the cytoplasm. Fis1p is the first integral membrane protein shown to participate in a eukaryotic membrane fission event. In a related study (Tieu, Q., and J. Nunnari. 2000. J. Cell Biol. 151:353-365), it was shown that the FIS2 gene product (called Mdv1p) colocalizes with Dnm1p on mitochondria. Genetic and morphological evidence indicate that Fis1p, but not Mdv1p, function is required for the proper assembly and distribution of Dnm1p-containing fission complexes on mitochondrial tubules. We propose that mitochondrial fission in yeast is a multi-step process, and that membrane-bound Fis1p is required for the proper assembly, membrane distribution, and function of Dnm1p-containing complexes during fission.

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Dnm1p and Fzo1p act in opposing fission and fusion pathways to maintain the yeast mitochondrial network. Ongoing fission and fusion events maintain a tubular mitochondrial network in wild-type yeast cells (middle). Loss of the Dnm1p GTPase (dnm1Δ) leads to net formation due to unopposed mitochondrial tip fusion (left); loss of the Fzo1p GTPase (fzo1Δ) leads to fragmentation due to unopposed mitochondrial fission (right).
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Figure 1: Dnm1p and Fzo1p act in opposing fission and fusion pathways to maintain the yeast mitochondrial network. Ongoing fission and fusion events maintain a tubular mitochondrial network in wild-type yeast cells (middle). Loss of the Dnm1p GTPase (dnm1Δ) leads to net formation due to unopposed mitochondrial tip fusion (left); loss of the Fzo1p GTPase (fzo1Δ) leads to fragmentation due to unopposed mitochondrial fission (right).

Mentions: In Saccharomyces cerevisiae, two evolutionarily conserved GTPases act on the outer mitochondrial membrane to regulate opposing fission and fusion reactions (Fig. 1) (Hales and Fuller 1997; Hermann and Shaw 1998; Otsuga et al. 1998; Bleazard et al. 1999; Labrousse et al. 1999; Sesaki and Jensen 1999). Fission is regulated by the dynamin-related GTPase Dnm1p, which assembles on mitochondrial tubules at sites of future division (Otsuga et al. 1998; Bleazard et al. 1999; Sesaki and Jensen 1999). dnm1 mutations block mitochondrial fission and lead to formation of interconnected nets due to ongoing tip fusion (Fig. 1, left). This net formation does not affect mitochondrial function, mitochondrial DNA (mtDNA) maintenance, or mitochondrial transport into buds during division (Otsuga et al. 1998; Bleazard et al. 1999). Conversely, fusion is regulated by the Fzo1p transmembrane GTPase (Hermann et al. 1998; Rapaport et al. 1998). In fzo1 mutant strains, mitochondrial fusion is blocked and tubules fragment due to unopposed mitochondrial fission (Fig. 1, right). As a secondary consequence of this fragmentation, mtDNA is lost and the resulting respiratory-deficient fzo1 cells fail to grow on the nonfermentable carbon source glycerol (Hermann et al. 1998).


Dnm1p GTPase-mediated mitochondrial fission is a multi-step process requiring the novel integral membrane component Fis1p.

Mozdy AD, McCaffery JM, Shaw JM - J. Cell Biol. (2000)

Dnm1p and Fzo1p act in opposing fission and fusion pathways to maintain the yeast mitochondrial network. Ongoing fission and fusion events maintain a tubular mitochondrial network in wild-type yeast cells (middle). Loss of the Dnm1p GTPase (dnm1Δ) leads to net formation due to unopposed mitochondrial tip fusion (left); loss of the Fzo1p GTPase (fzo1Δ) leads to fragmentation due to unopposed mitochondrial fission (right).
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2192649&req=5

Figure 1: Dnm1p and Fzo1p act in opposing fission and fusion pathways to maintain the yeast mitochondrial network. Ongoing fission and fusion events maintain a tubular mitochondrial network in wild-type yeast cells (middle). Loss of the Dnm1p GTPase (dnm1Δ) leads to net formation due to unopposed mitochondrial tip fusion (left); loss of the Fzo1p GTPase (fzo1Δ) leads to fragmentation due to unopposed mitochondrial fission (right).
Mentions: In Saccharomyces cerevisiae, two evolutionarily conserved GTPases act on the outer mitochondrial membrane to regulate opposing fission and fusion reactions (Fig. 1) (Hales and Fuller 1997; Hermann and Shaw 1998; Otsuga et al. 1998; Bleazard et al. 1999; Labrousse et al. 1999; Sesaki and Jensen 1999). Fission is regulated by the dynamin-related GTPase Dnm1p, which assembles on mitochondrial tubules at sites of future division (Otsuga et al. 1998; Bleazard et al. 1999; Sesaki and Jensen 1999). dnm1 mutations block mitochondrial fission and lead to formation of interconnected nets due to ongoing tip fusion (Fig. 1, left). This net formation does not affect mitochondrial function, mitochondrial DNA (mtDNA) maintenance, or mitochondrial transport into buds during division (Otsuga et al. 1998; Bleazard et al. 1999). Conversely, fusion is regulated by the Fzo1p transmembrane GTPase (Hermann et al. 1998; Rapaport et al. 1998). In fzo1 mutant strains, mitochondrial fusion is blocked and tubules fragment due to unopposed mitochondrial fission (Fig. 1, right). As a secondary consequence of this fragmentation, mtDNA is lost and the resulting respiratory-deficient fzo1 cells fail to grow on the nonfermentable carbon source glycerol (Hermann et al. 1998).

Bottom Line: Nunnari. 2000.Genetic and morphological evidence indicate that Fis1p, but not Mdv1p, function is required for the proper assembly and distribution of Dnm1p-containing fission complexes on mitochondrial tubules.We propose that mitochondrial fission in yeast is a multi-step process, and that membrane-bound Fis1p is required for the proper assembly, membrane distribution, and function of Dnm1p-containing complexes during fission.

View Article: PubMed Central - PubMed

Affiliation: Department of Biology, University of Utah, Salt Lake City, Utah 84112, USA.

ABSTRACT
Yeast Dnm1p is a soluble, dynamin-related GTPase that assembles on the outer mitochondrial membrane at sites where organelle division occurs. Although these Dnm1p-containing complexes are thought to trigger constriction and fission, little is known about their composition and assembly, and molecules required for their membrane recruitment have not been isolated. Using a genetic approach, we identified two new genes in the fission pathway, FIS1 and FIS2. FIS1 encodes a novel, outer mitochondrial membrane protein with its amino terminus exposed to the cytoplasm. Fis1p is the first integral membrane protein shown to participate in a eukaryotic membrane fission event. In a related study (Tieu, Q., and J. Nunnari. 2000. J. Cell Biol. 151:353-365), it was shown that the FIS2 gene product (called Mdv1p) colocalizes with Dnm1p on mitochondria. Genetic and morphological evidence indicate that Fis1p, but not Mdv1p, function is required for the proper assembly and distribution of Dnm1p-containing fission complexes on mitochondrial tubules. We propose that mitochondrial fission in yeast is a multi-step process, and that membrane-bound Fis1p is required for the proper assembly, membrane distribution, and function of Dnm1p-containing complexes during fission.

Show MeSH
Related in: MedlinePlus