9kfe

Structural highlights

Function

FZO1_YEAST Essential transmembrane GTPase, which mediates mitochondrial fusion (PubMed:10562274, PubMed:11266460, PubMed:15297626, PubMed:15760898, PubMed:16624808, PubMed:19812251, PubMed:21385840, PubMed:21502136, PubMed:23317502, PubMed:27253069, PubMed:9685359, PubMed:9786948). Fusion proceeds through several steps; first mitochondria are tethered together, then brought into close contact, followed by the formation of a docking ring around contact areas, and finally membrane fusion (PubMed:27253069). Fusion of mitochondria occurs in many cell types and constitutes an important step in mitochondrial morphology, which is balanced between fusion and fission, mediated by FZO1 and DNM1, respectively (PubMed:10562274). Functions antagonistically with DNM1 (PubMed:10562274). Probably acts by forming membrane contact sites that mediate mitochondrial membrane fusion (PubMed:27253069). Mitochondrial docking and fusion requires GTP hydrolysis (PubMed:15297626, PubMed:19812251, PubMed:27253069). Mitochondrial fusion also promotes increased lifespan.^{[1] [2] [3] [4] [5] [6] [7] [8] [9] [10] [11] [12]}

References

1. ↑ Sesaki H, Jensen RE. Division versus fusion: Dnm1p and Fzo1p antagonistically regulate mitochondrial shape. J Cell Biol. 1999 Nov 15;147(4):699-706. PMID:10562274 doi:10.1083/jcb.147.4.699
2. ↑ Fritz S, Rapaport D, Klanner E, Neupert W, Westermann B. Connection of the mitochondrial outer and inner membranes by Fzo1 is critical for organellar fusion. J Cell Biol. 2001 Feb 19;152(4):683-92. PMID:11266460 doi:10.1083/jcb.152.4.683
3. ↑ Meeusen S, McCaffery JM, Nunnari J. Mitochondrial fusion intermediates revealed in vitro. Science. 2004 Sep 17;305(5691):1747-52. PMID:15297626 doi:10.1126/science.1100612
4. ↑ Neutzner A, Youle RJ. Instability of the mitofusin Fzo1 regulates mitochondrial morphology during the mating response of the yeast Saccharomyces cerevisiae. J Biol Chem. 2005 May 13;280(19):18598-603. PMID:15760898 doi:10.1074/jbc.M500807200
5. ↑ Amiott EA, Cohen MM, Saint-Georges Y, Weissman AM, Shaw JM. A mutation associated with CMT2A neuropathy causes defects in Fzo1 GTP hydrolysis, ubiquitylation, and protein turnover. Mol Biol Cell. 2009 Dec;20(23):5026-35. PMID:19812251 doi:10.1091/mbc.e09-07-0622
6. ↑ Hammermeister M, Schödel K, Westermann B. Mdm36 is a mitochondrial fission-promoting protein in Saccharomyces cerevisiae. Mol Biol Cell. 2010 Jul 15;21(14):2443-52. PMID:20505073 doi:10.1091/mbc.e10-02-0096
7. ↑ Palermo V, Falcone C, Calvani M, Mazzoni C. Acetyl-L-carnitine protects yeast cells from apoptosis and aging and inhibits mitochondrial fission. Aging Cell. 2010 Aug;9(4):570-9. PMID:20550520 doi:10.1111/j.1474-9726.2010.00587.x
8. ↑ Anton F, Fres JM, Schauss A, Pinson B, Praefcke GJ, Langer T, Escobar-Henriques M. Ugo1 and Mdm30 act sequentially during Fzo1-mediated mitochondrial outer membrane fusion. J Cell Sci. 2011 Apr 1;124(Pt 7):1126-35. PMID:21385840 doi:10.1242/jcs.073080
9. ↑ Fernández-Cid A, Riera A, Herrero P, Moreno F. Glucose levels regulate the nucleo-mitochondrial distribution of Mig2. Mitochondrion. 2012 May;12(3):370-80. PMID:22353369 doi:10.1016/j.mito.2012.02.001
10. ↑ Brandt T, Cavellini L, Kühlbrandt W, Cohen MM. A mitofusin-dependent docking ring complex triggers mitochondrial fusion in vitro. Elife. 2016 Jun 2;5:e14618. PMID:27253069 doi:10.7554/eLife.14618
11. ↑ Rapaport D, Brunner M, Neupert W, Westermann B. Fzo1p is a mitochondrial outer membrane protein essential for the biogenesis of functional mitochondria in Saccharomyces cerevisiae. J Biol Chem. 1998 Aug 7;273(32):20150-5. PMID:9685359 doi:10.1074/jbc.273.32.20150
12. ↑ Hermann GJ, Thatcher JW, Mills JP, Hales KG, Fuller MT, Nunnari J, Shaw JM. Mitochondrial fusion in yeast requires the transmembrane GTPase Fzo1p. J Cell Biol. 1998 Oct 19;143(2):359-73. PMID:9786948 doi:10.1083/jcb.143.2.359