Conformational changes in Dnm1 support a contractile mechanism for mitochondrial fission

Jason A. Mears, Laura L. Lackner, Shunming Fang, Elena Ingerman, Jodi Nunnari, Jenny E. Hinshaw

Research output: Contribution to journalArticle

230 Citations (Scopus)

Abstract

Mitochondria are dynamic organelles that undergo cycles of fission and fusion. The yeast dynamin-related protein Dnm1 has been localized to sites of mitochondrial division. Using cryo-EM, we have determined the three-dimensional (3D) structure of Dnm1 in a GTP-bound state. The 3D map showed that Dnm1 adopted a unique helical assembly when compared with dynamin, which is involved in vesicle scission during endocytosis. Upon GTP hydrolysis, Dnm1 constricted liposomes and subsequently dissociated from the lipid bilayer. The magnitude of Dnm1 constriction was substantially larger than the decrease in diameter previously reported for dynamin. We postulate that the larger conformational change is mediated by a flexible Dnm1 structure that has limited interaction with the underlying bilayer. Our structural studies support the idea that Dnm1 has a mechanochemical role during mitochondrial division.

Original languageEnglish (US)
Pages (from-to)20-27
Number of pages8
JournalNature Structural and Molecular Biology
Volume18
Issue number1
DOIs
StatePublished - Jan 2011

Fingerprint

Mitochondrial Dynamics
Dynamins
Guanosine Triphosphate
Lipid Bilayers
Endocytosis
Constriction
Liposomes
Organelles
Mitochondria
Hydrolysis
Yeasts
Proteins

ASJC Scopus subject areas

  • Structural Biology
  • Molecular Biology

Cite this

Mears, J. A., Lackner, L. L., Fang, S., Ingerman, E., Nunnari, J., & Hinshaw, J. E. (2011). Conformational changes in Dnm1 support a contractile mechanism for mitochondrial fission. Nature Structural and Molecular Biology, 18(1), 20-27. https://doi.org/10.1038/nsmb.1949

Conformational changes in Dnm1 support a contractile mechanism for mitochondrial fission. / Mears, Jason A.; Lackner, Laura L.; Fang, Shunming; Ingerman, Elena; Nunnari, Jodi; Hinshaw, Jenny E.

In: Nature Structural and Molecular Biology, Vol. 18, No. 1, 01.2011, p. 20-27.

Research output: Contribution to journalArticle

Mears, JA, Lackner, LL, Fang, S, Ingerman, E, Nunnari, J & Hinshaw, JE 2011, 'Conformational changes in Dnm1 support a contractile mechanism for mitochondrial fission', Nature Structural and Molecular Biology, vol. 18, no. 1, pp. 20-27. https://doi.org/10.1038/nsmb.1949
Mears, Jason A. ; Lackner, Laura L. ; Fang, Shunming ; Ingerman, Elena ; Nunnari, Jodi ; Hinshaw, Jenny E. / Conformational changes in Dnm1 support a contractile mechanism for mitochondrial fission. In: Nature Structural and Molecular Biology. 2011 ; Vol. 18, No. 1. pp. 20-27.
@article{68f3d1945fc04b9e914e89d91f4cc676,
title = "Conformational changes in Dnm1 support a contractile mechanism for mitochondrial fission",
abstract = "Mitochondria are dynamic organelles that undergo cycles of fission and fusion. The yeast dynamin-related protein Dnm1 has been localized to sites of mitochondrial division. Using cryo-EM, we have determined the three-dimensional (3D) structure of Dnm1 in a GTP-bound state. The 3D map showed that Dnm1 adopted a unique helical assembly when compared with dynamin, which is involved in vesicle scission during endocytosis. Upon GTP hydrolysis, Dnm1 constricted liposomes and subsequently dissociated from the lipid bilayer. The magnitude of Dnm1 constriction was substantially larger than the decrease in diameter previously reported for dynamin. We postulate that the larger conformational change is mediated by a flexible Dnm1 structure that has limited interaction with the underlying bilayer. Our structural studies support the idea that Dnm1 has a mechanochemical role during mitochondrial division.",
author = "Mears, {Jason A.} and Lackner, {Laura L.} and Shunming Fang and Elena Ingerman and Jodi Nunnari and Hinshaw, {Jenny E.}",
year = "2011",
month = "1",
doi = "10.1038/nsmb.1949",
language = "English (US)",
volume = "18",
pages = "20--27",
journal = "Nature Structural and Molecular Biology",
issn = "1545-9993",
publisher = "Nature Publishing Group",
number = "1",

}

TY - JOUR

T1 - Conformational changes in Dnm1 support a contractile mechanism for mitochondrial fission

AU - Mears, Jason A.

AU - Lackner, Laura L.

AU - Fang, Shunming

AU - Ingerman, Elena

AU - Nunnari, Jodi

AU - Hinshaw, Jenny E.

PY - 2011/1

Y1 - 2011/1

N2 - Mitochondria are dynamic organelles that undergo cycles of fission and fusion. The yeast dynamin-related protein Dnm1 has been localized to sites of mitochondrial division. Using cryo-EM, we have determined the three-dimensional (3D) structure of Dnm1 in a GTP-bound state. The 3D map showed that Dnm1 adopted a unique helical assembly when compared with dynamin, which is involved in vesicle scission during endocytosis. Upon GTP hydrolysis, Dnm1 constricted liposomes and subsequently dissociated from the lipid bilayer. The magnitude of Dnm1 constriction was substantially larger than the decrease in diameter previously reported for dynamin. We postulate that the larger conformational change is mediated by a flexible Dnm1 structure that has limited interaction with the underlying bilayer. Our structural studies support the idea that Dnm1 has a mechanochemical role during mitochondrial division.

AB - Mitochondria are dynamic organelles that undergo cycles of fission and fusion. The yeast dynamin-related protein Dnm1 has been localized to sites of mitochondrial division. Using cryo-EM, we have determined the three-dimensional (3D) structure of Dnm1 in a GTP-bound state. The 3D map showed that Dnm1 adopted a unique helical assembly when compared with dynamin, which is involved in vesicle scission during endocytosis. Upon GTP hydrolysis, Dnm1 constricted liposomes and subsequently dissociated from the lipid bilayer. The magnitude of Dnm1 constriction was substantially larger than the decrease in diameter previously reported for dynamin. We postulate that the larger conformational change is mediated by a flexible Dnm1 structure that has limited interaction with the underlying bilayer. Our structural studies support the idea that Dnm1 has a mechanochemical role during mitochondrial division.

UR - http://www.scopus.com/inward/record.url?scp=78650987611&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=78650987611&partnerID=8YFLogxK

U2 - 10.1038/nsmb.1949

DO - 10.1038/nsmb.1949

M3 - Article

C2 - 21170049

AN - SCOPUS:78650987611

VL - 18

SP - 20

EP - 27

JO - Nature Structural and Molecular Biology

JF - Nature Structural and Molecular Biology

SN - 1545-9993

IS - 1

ER -