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Structural Heterogeneity of Mitochondria Induced by the Microtubule Cytoskeleton.

Sukhorukov VM, Meyer-Hermann M - Sci Rep (2015)

Bottom Line: The model reproduces the full spectrum of experimentally found mitochondrial configurations.In centrosome-organized cells, the chondriome is predicted to develop strong structural inhomogeneity between the cell center and the periphery.We propose that it is the combination of the two processes that defines synergistically the mitochondrial structure, providing the cell with ample capabilities for its regulative adaptation.

View Article: PubMed Central - PubMed

Affiliation: Department of Systems Immunology and Braunschweig Integrated Centre of Systems Biology, Helmholtz Centre for Infection Research, Inhoffenstr. 7, 38124 Braunschweig, Germany.

ABSTRACT
By events of fusion and fission mitochondria generate a partially interconnected, irregular network of poorly specified architecture. Here, its organization is examined theoretically by taking into account the physical association of mitochondria with microtubules. Parameters of the cytoskeleton mesh are derived from the mechanics of single fibers. The model of the mitochondrial reticulum is formulated in terms of a dynamic spatial graph. The graph dynamics is modulated by the density of microtubules and their crossings. The model reproduces the full spectrum of experimentally found mitochondrial configurations. In centrosome-organized cells, the chondriome is predicted to develop strong structural inhomogeneity between the cell center and the periphery. An integrated analysis of the cytoskeletal and the mitochondrial components reveals that the structure of the reticulum depends on the balance between anterograde and retrograde motility of mitochondria on microtubules, in addition to fission and fusion. We propose that it is the combination of the two processes that defines synergistically the mitochondrial structure, providing the cell with ample capabilities for its regulative adaptation.

No MeSH data available.


Related in: MedlinePlus

Network structure of the mitochondrial reticulum.(A) Length of mitochondria segments obtained as solutions of thegraph-based model (Eqs. (10, 11, 12)) in dependence on the radial distance and the fusion tofission ratio γ. Black lines are cross-sections at distancesof 4, 8, and 12 μm from the cell center. The blue line isat γ = 0.1. (B) Node abundances as fractionsof the total system size 2Q1(r) with the samedependencies as in A: free ends u1 (red), bulk nodesu2 (green) and branching nodes u3(blue) are obtained as solutions of Eqs. (10, 11, 12). (C) Distribution of thecluster sizes assuming uniform mitochondrial occupancy of the MTs(ψ = 0) forγ = 0.01 (left), 0.1 (center) and 1(right) at a distance of 4 (dark blue), 8 (grey), and12 μm (light blue) from the cell center. (D)Distribution of cluster sizes for the intermediate fusion/fission ratioγ = 0.1 at distances of 4 (dark blue), 8(grey), and 12 μm (light blue) from the cellcenter, assuming a finite drift of mitochondria towards the centrosome(ψ = −0.2, upper panel) andtowards the cell periphery (ψ = 0.2, lowerpanel). (E) Radially resolved fraction of the largest cluster in thechondriome for a perinuclear (ψ = −0.2,rectangles), a neutral (ψ = 0,circles) and a peripheral (ψ = 0.2,triangles) accumulation of mitochondria along the MTs. An intermediatefusion/fission rate constant γ = 0.1 was used(solid lines and marks). For a balanced radial drift(ψ = 0), the sensitivity to the fusion tofission ratio is shown as shaded area by varying betweenγ = 0.01 (lower edge) andγ = 1 (upper edge). Results in(A,B) are generated with the deterministic model of mitochondria,and in (C,D) with the stochastic model.
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f3: Network structure of the mitochondrial reticulum.(A) Length of mitochondria segments obtained as solutions of thegraph-based model (Eqs. (10, 11, 12)) in dependence on the radial distance and the fusion tofission ratio γ. Black lines are cross-sections at distancesof 4, 8, and 12 μm from the cell center. The blue line isat γ = 0.1. (B) Node abundances as fractionsof the total system size 2Q1(r) with the samedependencies as in A: free ends u1 (red), bulk nodesu2 (green) and branching nodes u3(blue) are obtained as solutions of Eqs. (10, 11, 12). (C) Distribution of thecluster sizes assuming uniform mitochondrial occupancy of the MTs(ψ = 0) forγ = 0.01 (left), 0.1 (center) and 1(right) at a distance of 4 (dark blue), 8 (grey), and12 μm (light blue) from the cell center. (D)Distribution of cluster sizes for the intermediate fusion/fission ratioγ = 0.1 at distances of 4 (dark blue), 8(grey), and 12 μm (light blue) from the cellcenter, assuming a finite drift of mitochondria towards the centrosome(ψ = −0.2, upper panel) andtowards the cell periphery (ψ = 0.2, lowerpanel). (E) Radially resolved fraction of the largest cluster in thechondriome for a perinuclear (ψ = −0.2,rectangles), a neutral (ψ = 0,circles) and a peripheral (ψ = 0.2,triangles) accumulation of mitochondria along the MTs. An intermediatefusion/fission rate constant γ = 0.1 was used(solid lines and marks). For a balanced radial drift(ψ = 0), the sensitivity to the fusion tofission ratio is shown as shaded area by varying betweenγ = 0.01 (lower edge) andγ = 1 (upper edge). Results in(A,B) are generated with the deterministic model of mitochondria,and in (C,D) with the stochastic model.

Mentions: Solutions (Fig. 3A,B) of the deterministic model (Eqs. (10, 11, 12))characterize the network on the level of nodes ui(r,γ, ψ) with node degree i = 1,2, 3 (Fig. 1A) and segments (defined in Fig.1B). A characterization by physically disconnected clusters (defined inFig. 1C) requires a more detailed stochastic formulation,achieved here with an agent-based simulation of the same system. In the latter,mitochondria are represented explicitly in a virtual cell and subjected to fissionand fusion events corresponding to Eqs. (3) and (4). (Methods,Stochastic model of mitochondrial reticulum).


Structural Heterogeneity of Mitochondria Induced by the Microtubule Cytoskeleton.

Sukhorukov VM, Meyer-Hermann M - Sci Rep (2015)

Network structure of the mitochondrial reticulum.(A) Length of mitochondria segments obtained as solutions of thegraph-based model (Eqs. (10, 11, 12)) in dependence on the radial distance and the fusion tofission ratio γ. Black lines are cross-sections at distancesof 4, 8, and 12 μm from the cell center. The blue line isat γ = 0.1. (B) Node abundances as fractionsof the total system size 2Q1(r) with the samedependencies as in A: free ends u1 (red), bulk nodesu2 (green) and branching nodes u3(blue) are obtained as solutions of Eqs. (10, 11, 12). (C) Distribution of thecluster sizes assuming uniform mitochondrial occupancy of the MTs(ψ = 0) forγ = 0.01 (left), 0.1 (center) and 1(right) at a distance of 4 (dark blue), 8 (grey), and12 μm (light blue) from the cell center. (D)Distribution of cluster sizes for the intermediate fusion/fission ratioγ = 0.1 at distances of 4 (dark blue), 8(grey), and 12 μm (light blue) from the cellcenter, assuming a finite drift of mitochondria towards the centrosome(ψ = −0.2, upper panel) andtowards the cell periphery (ψ = 0.2, lowerpanel). (E) Radially resolved fraction of the largest cluster in thechondriome for a perinuclear (ψ = −0.2,rectangles), a neutral (ψ = 0,circles) and a peripheral (ψ = 0.2,triangles) accumulation of mitochondria along the MTs. An intermediatefusion/fission rate constant γ = 0.1 was used(solid lines and marks). For a balanced radial drift(ψ = 0), the sensitivity to the fusion tofission ratio is shown as shaded area by varying betweenγ = 0.01 (lower edge) andγ = 1 (upper edge). Results in(A,B) are generated with the deterministic model of mitochondria,and in (C,D) with the stochastic model.
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4565121&req=5

f3: Network structure of the mitochondrial reticulum.(A) Length of mitochondria segments obtained as solutions of thegraph-based model (Eqs. (10, 11, 12)) in dependence on the radial distance and the fusion tofission ratio γ. Black lines are cross-sections at distancesof 4, 8, and 12 μm from the cell center. The blue line isat γ = 0.1. (B) Node abundances as fractionsof the total system size 2Q1(r) with the samedependencies as in A: free ends u1 (red), bulk nodesu2 (green) and branching nodes u3(blue) are obtained as solutions of Eqs. (10, 11, 12). (C) Distribution of thecluster sizes assuming uniform mitochondrial occupancy of the MTs(ψ = 0) forγ = 0.01 (left), 0.1 (center) and 1(right) at a distance of 4 (dark blue), 8 (grey), and12 μm (light blue) from the cell center. (D)Distribution of cluster sizes for the intermediate fusion/fission ratioγ = 0.1 at distances of 4 (dark blue), 8(grey), and 12 μm (light blue) from the cellcenter, assuming a finite drift of mitochondria towards the centrosome(ψ = −0.2, upper panel) andtowards the cell periphery (ψ = 0.2, lowerpanel). (E) Radially resolved fraction of the largest cluster in thechondriome for a perinuclear (ψ = −0.2,rectangles), a neutral (ψ = 0,circles) and a peripheral (ψ = 0.2,triangles) accumulation of mitochondria along the MTs. An intermediatefusion/fission rate constant γ = 0.1 was used(solid lines and marks). For a balanced radial drift(ψ = 0), the sensitivity to the fusion tofission ratio is shown as shaded area by varying betweenγ = 0.01 (lower edge) andγ = 1 (upper edge). Results in(A,B) are generated with the deterministic model of mitochondria,and in (C,D) with the stochastic model.
Mentions: Solutions (Fig. 3A,B) of the deterministic model (Eqs. (10, 11, 12))characterize the network on the level of nodes ui(r,γ, ψ) with node degree i = 1,2, 3 (Fig. 1A) and segments (defined in Fig.1B). A characterization by physically disconnected clusters (defined inFig. 1C) requires a more detailed stochastic formulation,achieved here with an agent-based simulation of the same system. In the latter,mitochondria are represented explicitly in a virtual cell and subjected to fissionand fusion events corresponding to Eqs. (3) and (4). (Methods,Stochastic model of mitochondrial reticulum).

Bottom Line: The model reproduces the full spectrum of experimentally found mitochondrial configurations.In centrosome-organized cells, the chondriome is predicted to develop strong structural inhomogeneity between the cell center and the periphery.We propose that it is the combination of the two processes that defines synergistically the mitochondrial structure, providing the cell with ample capabilities for its regulative adaptation.

View Article: PubMed Central - PubMed

Affiliation: Department of Systems Immunology and Braunschweig Integrated Centre of Systems Biology, Helmholtz Centre for Infection Research, Inhoffenstr. 7, 38124 Braunschweig, Germany.

ABSTRACT
By events of fusion and fission mitochondria generate a partially interconnected, irregular network of poorly specified architecture. Here, its organization is examined theoretically by taking into account the physical association of mitochondria with microtubules. Parameters of the cytoskeleton mesh are derived from the mechanics of single fibers. The model of the mitochondrial reticulum is formulated in terms of a dynamic spatial graph. The graph dynamics is modulated by the density of microtubules and their crossings. The model reproduces the full spectrum of experimentally found mitochondrial configurations. In centrosome-organized cells, the chondriome is predicted to develop strong structural inhomogeneity between the cell center and the periphery. An integrated analysis of the cytoskeletal and the mitochondrial components reveals that the structure of the reticulum depends on the balance between anterograde and retrograde motility of mitochondria on microtubules, in addition to fission and fusion. We propose that it is the combination of the two processes that defines synergistically the mitochondrial structure, providing the cell with ample capabilities for its regulative adaptation.

No MeSH data available.


Related in: MedlinePlus