Mechanisms of Mitochondrial Fission and Fusion

Overview

Journal Cold Spring Harb Perspect Biol

Specialties Biology
Molecular Biology

Date 2013 Jun 5

PMID 23732471

Citations 398

Authors

Alexander M van der Bliek

Qinfang Shen

Sumihiro Kawajiri

Affiliations

Soon will be listed here.

Abstract

Mitochondria continually change shape through the combined actions of fission, fusion, and movement along cytoskeletal tracks. The lengths of mitochondria and the degree to which they form closed networks are determined by the balance between fission and fusion rates. These rates are influenced by metabolic and pathogenic conditions inside mitochondria and by their cellular environment. Fission and fusion are important for growth, for mitochondrial redistribution, and for maintenance of a healthy mitochondrial network. In addition, mitochondrial fission and fusion play prominent roles in disease-related processes such as apoptosis and mitophagy. Three members of the Dynamin family are key components of the fission and fusion machineries. Their functions are controlled by different sets of adaptor proteins on the surface of mitochondria and by a range of regulatory processes. Here, we review what is known about these proteins and the processes that regulate their actions.

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References

Braschi E, Zunino R, McBride H . MAPL is a new mitochondrial SUMO E3 ligase that regulates mitochondrial fission. EMBO Rep. 2009; 10(7):748-54. PMC: 2727426. DOI: 10.1038/embor.2009.86. View

Bleazard W, McCaffery J, King E, Bale S, Mozdy A, Tieu Q . The dynamin-related GTPase Dnm1 regulates mitochondrial fission in yeast. Nat Cell Biol. 1999; 1(5):298-304. PMC: 3739991. DOI: 10.1038/13014. View

Olichon A, Emorine L, Descoins E, Pelloquin L, Brichese L, Gas N . The human dynamin-related protein OPA1 is anchored to the mitochondrial inner membrane facing the inter-membrane space. FEBS Lett. 2002; 523(1-3):171-6. DOI: 10.1016/s0014-5793(02)02985-x. View

De Vos K, Allan V, Grierson A, Sheetz M . Mitochondrial function and actin regulate dynamin-related protein 1-dependent mitochondrial fission. Curr Biol. 2005; 15(7):678-83. DOI: 10.1016/j.cub.2005.02.064. View

Durr M, Escobar-Henriques M, Merz S, Geimer S, Langer T, Westermann B . Nonredundant roles of mitochondria-associated F-box proteins Mfb1 and Mdm30 in maintenance of mitochondrial morphology in yeast. Mol Biol Cell. 2006; 17(9):3745-55. PMC: 1593156. DOI: 10.1091/mbc.e06-01-0053. View

Frezza C, Cipolat S, Martins de Brito O, Micaroni M, Beznoussenko G, Rudka T . OPA1 controls apoptotic cristae remodeling independently from mitochondrial fusion. Cell. 2006; 126(1):177-89. DOI: 10.1016/j.cell.2006.06.025. View

Cassidy-Stone A, Chipuk J, Ingerman E, Song C, Yoo C, Kuwana T . Chemical inhibition of the mitochondrial division dynamin reveals its role in Bax/Bak-dependent mitochondrial outer membrane permeabilization. Dev Cell. 2008; 14(2):193-204. PMC: 2267902. DOI: 10.1016/j.devcel.2007.11.019. View

Macia E, Ehrlich M, Massol R, Boucrot E, Brunner C, Kirchhausen T . Dynasore, a cell-permeable inhibitor of dynamin. Dev Cell. 2006; 10(6):839-50. DOI: 10.1016/j.devcel.2006.04.002. View

Mozdy A, McCaffery J, Shaw J . Dnm1p GTPase-mediated mitochondrial fission is a multi-step process requiring the novel integral membrane component Fis1p. J Cell Biol. 2000; 151(2):367-80. PMC: 2192649. DOI: 10.1083/jcb.151.2.367. View

10.

Sesaki H, Jensen R . Ugo1p links the Fzo1p and Mgm1p GTPases for mitochondrial fusion. J Biol Chem. 2004; 279(27):28298-303. DOI: 10.1074/jbc.M401363200. View

11.

Frank S, Gaume B, Bergmann-Leitner E, Leitner W, Robert E, Catez F . The role of dynamin-related protein 1, a mediator of mitochondrial fission, in apoptosis. Dev Cell. 2001; 1(4):515-25. DOI: 10.1016/s1534-5807(01)00055-7. View

12.

van der Bliek A, Payne G . Dynamin subunit interactions revealed. Dev Cell. 2010; 18(5):687-8. PMC: 2880500. DOI: 10.1016/j.devcel.2010.05.001. View

13.

Liesa M, Palacin M, Zorzano A . Mitochondrial dynamics in mammalian health and disease. Physiol Rev. 2009; 89(3):799-845. DOI: 10.1152/physrev.00030.2008. View

14.

Lokireddy S, Wijesoma I, Teng S, Bonala S, Gluckman P, McFarlane C . The ubiquitin ligase Mul1 induces mitophagy in skeletal muscle in response to muscle-wasting stimuli. Cell Metab. 2012; 16(5):613-24. DOI: 10.1016/j.cmet.2012.10.005. View

15.

Iwasawa R, Mahul-Mellier A, Datler C, Pazarentzos E, Grimm S . Fis1 and Bap31 bridge the mitochondria-ER interface to establish a platform for apoptosis induction. EMBO J. 2010; 30(3):556-68. PMC: 3034017. DOI: 10.1038/emboj.2010.346. View

16.

Rambold A, Kostelecky B, Elia N, Lippincott-Schwartz J . Tubular network formation protects mitochondria from autophagosomal degradation during nutrient starvation. Proc Natl Acad Sci U S A. 2011; 108(25):10190-5. PMC: 3121813. DOI: 10.1073/pnas.1107402108. View

17.

Griffin E, Graumann J, Chan D . The WD40 protein Caf4p is a component of the mitochondrial fission machinery and recruits Dnm1p to mitochondria. J Cell Biol. 2005; 170(2):237-48. PMC: 2171414. DOI: 10.1083/jcb.200503148. View

18.

Twig G, Elorza A, Molina A, Mohamed H, Wikstrom J, Walzer G . Fission and selective fusion govern mitochondrial segregation and elimination by autophagy. EMBO J. 2008; 27(2):433-46. PMC: 2234339. DOI: 10.1038/sj.emboj.7601963. View

19.

Youle R, Narendra D . Mechanisms of mitophagy. Nat Rev Mol Cell Biol. 2010; 12(1):9-14. PMC: 4780047. DOI: 10.1038/nrm3028. View

20.

Rowland A, Voeltz G . Endoplasmic reticulum-mitochondria contacts: function of the junction. Nat Rev Mol Cell Biol. 2012; 13(10):607-25. PMC: 5111635. DOI: 10.1038/nrm3440. View