Dnm1p Gtpase-Mediated Mitochondrial Fission Is a Multi-Step Process Requiring the Novel Integral Membrane Component Fis1p

By A. Mozdy, J. McCaffery, J. Shaw. Journal of Cell Biology, 2000

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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.

Subfields: Molecular Biology

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Citations in the corpus

Dynamin-related protein Drp1 is required for mitochondrial division in mammalian cells. (2001, neutral): “One protein called Mdv1/Fis2/Gag3 is a WD-repeat protein that may serve as an adapter within the Dnm1 protein complex (Fekkes et al., 2000; Mozdy et al., 2000; Tieu and Nunnari, 2000).”
The dynamin-related GTPase Drp1 is required for embryonic and brain development in mice (2009, background): “Most Drp1 is cytosolic and is recruited to the surface of mitochondria by proteins such as Fis1p/Fis1, Mdv1p, Caf4p, and Num1p (Mozdy et al., 2000; Tieu and Nunnari, 2000; Cerveny et al., 2001; James et al., 2003; Yoon et al., 2003: Griffin et al., 2005; Cerveny et al., 2007b).”
Mechanisms of mitochondrial fission and fusion. (2013, background): “One of the fission proteins that came out of these screens is Fis1, which has two tetratrico peptide repeat (TPR) domains and a carboxy-terminal hydrophobic segment that anchors this protein in the mitochondrial outer membrane (Mozdy et al. 2000).”
Fis1, Mff, MiD49, and MiD51 mediate Drp1 recruitment in mitochondrial fission (2013, background): “The yeast Drp1 orthologue, Dnm1, requires Fis1 to localize to mitochondria (Fekkes et al., 2000; Mozdy et al., 2000; Tieu and Nunnari, 2000).”
Dnm1 forms spirals that are structurally tailored to fit mitochondria (2005, background): “…mitochondrial division, however, is also regulated by and requires the actions of the outer membrane protein Fis1 and the WD repeat adaptor proteins Mdv1 and Caf4 (Fekkes et al., 2000; Mozdy et al., 2000; Tieu and Nunnari, 2000; Cerveny et al., 2001; Tieu et al., 2002; Suzuki et al., 2005).”
MiD49 and MiD51, new components of the mitochondrial fission machinery (2011, background): “In yeast, Dnm1 is recruited to mitochondria by Fis1 and the effector proteins Mdv1 and Caf4 to drive mitochondrial fission (Mozdy et al, 2000; Tieu & Nunnari, 2000; Griffin et al, 2005; Koirala et al, 2010).”
Spatial and temporal association of Bax with mitochondrial fission sites, Drp1, and Mfn2 during apoptosis (2002, methodology): “YFP- Bax and mitchondrial scission foci | Karbowski et al. 935 Fis1 and YFP-OMP25 circumscribed mitochondria completely in healthy cells, whereas YFP-synaptojanin 2A was mostly cytosolic.”
The Mitochondrial Protein hFis1 Regulates Mitochondrial Fission in Mammalian Cells through an Interaction with the Dynamin-Like Protein DLP1 (2003, background): “Morphological studies found that Dnm1p and Mdv1p colocalized on mitochondrial tubules as punctate spots, and in the absence of Fis1p, the size and number of these Dnm1p-containing structures were grossly altered ( 15 , 25).”
Roles of the mammalian mitochondrial fission and fusion mediators Fis1, Drp1, and Opa1 in apoptosis. (2004, background): “, 1999), Fis1 (Mozdy et al., 2000; Jakobs et al., 2003), and up to six other gene products in yeast (Dimmer et al.”
Mitophagy and Alzheimer’s disease: cellular and molecular mechanisms (2017, background): “Mitochondrial fission and fusion are controlled by specialized proteins such as Fis1 and Drp1 [73,74] and Opa1 [75], respectively; the levels of each of these proteins determine the amount of fission and fusion occurring.”