Dnm1 forms spirals that are structurally tailored to fit mitochondria

By Elena Ingerman, Edward M. Perkins, M. Marino, J. Mears, J. McCaffery, J. Hinshaw, J. Nunnari. Journal of Cell Biology, 2005

614 citations recorded by the source corpus.

Dynamin-related proteins (DRPs) are large self-assembling GTPases whose common function is to regulate membrane dynamics in a variety of cellular processes. Dnm1, which is a yeast DRP (Drp1/Dlp1 in humans), is required for mitochondrial division, but its mechanism is unknown. We provide evidence that Dnm1 likely functions through self-assembly to drive the membrane constriction event that is associated with mitochondrial division. Two regulatory features of Dnm1 self-assembly were also identified. Dnm1 self-assembly proceeded through a rate-limiting nucleation step, and nucleotide hydrolysis by assembled Dnm1 structures was highly cooperative with respect to GTP. Dnm1 formed extended spirals, which possessed diameters greater than those of dynamin-1 spirals but whose sizes, remarkably, were equal to those of mitochondrial constriction sites in vivo. These data suggest that Dnm1 has evolved to form structures that fit the dimensions of mitochondria.

Subfields: Molecular Biology

View Paper: https://www.semanticscholar.org/paper/26cead825f30751fd3d323b720cb0ea1f2490100

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In Molecular Biology

1. B. Westermann
2. D. C. Chan
3. R. Youle
4. A. M. van der Bliek
5. M. Liesa
6. J. Nunnari
7. A. Suomalainen
8. D. Suen

Citations in the corpus

• Mitochondrial fusion and fission in cell life and death (2010, background): “These spirals have a diameter of 100 nm and fit in mitochondrial constrictions at division sites, which have a diameter of ∼100 nm in vivo”
• The dynamin-related GTPase Drp1 is required for embryonic and brain development in mice (2009, background): “The frequency of mitochondrial division was decreased by 17-fold spirals that wrap around mitochondria and pinches off their membranes as a mechanochemical enzyme (Yoon et al., 2001; Ingerman et al., 2005).”
• Mitochondrial fusion and fission in mammals. (2006, background): “Indeed, Dnm1 in vitro shows assembly-dependent GTP hydrolysis and is able to assemble into spirals with dimensions consistent with constricted mitochondrial tubules (Ingerman et al. 2005).”
• Mitochondrial dynamics in mammalian health and disease. (2009, background): “strict the mitochondrial tubule by DRP1 oligomers, which surround it, thereby forming a spiral ring around the scission site (133, 143, 273, 327).”
• Mechanisms of mitochondrial fission and fusion. (2013, background): “Instead of the 50 nm for Dynamin, these spirals have an average diameter of 120 nm (Ingerman et al. 2005; Mears et al. 2011).”
• The novel tail-anchored membrane protein Mff controls mitochondrial and peroxisomal fission in mammalian cells. (2008, background): “Mitochondrial dynamin proteins are called Drp1 in mammals and Dnm1 in yeast (van der Bliek, 1999).”
• Cellular and molecular mechanisms of mitochondrial function (2012, background): “43,44 New evidence has emerged regarding the outer membrane proteins that regulate Drp1 action at the mitochondrial surface and in turn control mitochondrial functionality.”
• Mitochondria: In Sickness and in Health (2012, background): “Evidence suggests that DRP1 divides mitochondria by forming helical structures that wrap around mitochondria (Ingerman et al., 2005; Labrousse et al., 1999; Yoon et al., 2001).”
• A new pathway for mitochondrial quality control: mitochondrial‐derived vesicles (2014, neutral): “The independence of Drp1 is consistent with the diameter of the yeast mitochondrial dynamin (Dnm1) ring limited to 100 nm, which would be too large to constrict an MDV neck (Ingerman et al, 2005).”
• Dynamin, a membrane remodelling GTPase (2012, background): “Furthermore, whereas the GTP binding and hydrolysis cycle of regulatory GTPases mediates the recruitment and release of effector proteins, the cellular function of DLPs is tightly coupled to the dimerization of their G domains and, at least for some of them, to their polymerizatio”
• Mitochondrial fragmentation in neurodegeneration (2008, background): “When it is bound to analogues of GTP that cannot be hydrolysed to GDP, Dnm1 assembles into ring and spiral-like structure”