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Cytoskeletal regulation of mitochondrial movements in myoblasts

Significance Statement

The study “Cytoskeletal regulation of mitochondrial movements in myoblasts” examined which cytoskeletal elements were primarily responsible for mitochondrial movements in muscle cells, and asked whether calcium could influence organelle motility.  The amount and distribution of mitochondria within muscle is influenced by energy supply and demand.  Long distances between organelles detract from the efficient diffusion of oxygen and metabolites which ultimately help muscle energy production.  Using live-cell imaging, we monitored mitochondrial movements and found that these organelles move primarily along microtubules tracks.  Moreover, we found that the displacement of mitochondria within muscle cells was regulated by the important signaling ion, calcium.  By understanding mitochondrial movements and the signaling events that regulate their dynamics, we can determine the underlying basis for organelle interactions, and the distribution of energy in muscle cells.

Figure 1: Mitochondrial movement within the cell, as governed by cytoskeletal elements.  Actin, microtubules, and intermediate filaments constitute the cellular cytoskeleton, whereas dynein and kinesin are the motor proteins for microtubules.  In response to stimuli, such as exercise, calcium is released from the sarcoplasmic reticulum, increasing the concentration of cytosolic calcium.  Elevated calcium binds to components of the motor protein, kinesin, inducing a conformational change in the protein that dissociates the complex from microtubules, halting mitochondrial movements.  Another vital set of signaling molecules, reactive oxygen species (ROS), is generated mainly by mitochondria in response to conditions such as aging and denervation.  Excessive production of ROS also reduces the motility of mitochondria within muscle cells.

Cytoskeletal regulation of mitochondrial movements in myoblasts

 

 

 

 

 

 

 

 

 

 

Journal Reference

Iqbal S, Hood DA.

Cytoskeleton (Hoboken). 2014 ;71(10):564-72.

School of Kinesiology and Health Science, York University, Toronto, Ontario, Canada; Muscle Health Research Centre, York University, Toronto, Ontario, Canada.

 

Abstract

Mitochondria are distributed in the cell to match the energy demands, and it is their interaction with the cytoskeleton that controls their movement and displacement. Our purpose was to determine which cytoskeletal components are primarily responsible for mitochondrial movement in muscle cells. Live-cell imaging was used to visualize mitochondrial dynamics in myoblasts. Destabilization of microtubules (MT) reduced the total path length and average speed traveled by mitochondria by 64-74%, whereas actin disruption only reduced these variables by 37-40%. Downregulation of the microtubule motor proteins, Kif5B and dynein, by siRNA resulted in decreases in the average speed of mitochondrial movements, by 30 to 40%. We observed a reduction in the average speed of mitochondrial movements (by 22 to 48%) under high calcium conditions. This attenuation in the presence of calcium was negated in cells pre-treated with siRNA targeted to the microtubule motor protein adaptor, Milton, suggesting that Milton is involved in mediating mitochondrial arrest in the presence of high calcium within muscle cells. Thus, we have demonstrated that, in myoblasts, mitochondria primarily move along microtubules tracks with the aid of the motor proteins Kif5B and dynein, in a manner which is inhibited by calcium. These observations will eventually help us understand organelle movements in more complex muscle systems, such as mature myotubes subjected to elevated calcium levels and contractile activity.

© 2014 Wiley Periodicals, Inc.

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