Thursday, 7 June 2018

Power grid protection of the muscle mitochondrial reticulum.

Brian Glancy, Lisa M. Hartnell, Christian A. Combs, Armel Femnou, Junhui Sun, Elizabeth Murphy,
Sriram Subramaniam and Robert S. Balaban.

Cellular mitochondrial networks allow for sharing of metabolites and proteins as well as mitochondrial DNA, and also provide a rapid conductive path for the distribution of potential energy.

However, this extensive coupling presents a major risk as local failures can also spread quickly over the entire network and compromise cellular energy conversion.

Like many power networks that physically segment elements with circuit breakers, similar strategies may be in place to protect cells with coupled mitochondrial networks from propagating local failures.

Using 2-to-4 month old mice, the authors demonstrate the existence a physically and electrically connected mitochondrial reticulum arranged into longitudinal subnetworks within the cardiac cell.

Each subnetworks comprises many mitochondria and subnetworks are linked through abundant contact sites at highly specific intermitochondrial junctions, IMJs.
(A junction is defined by the close apposition of both the inner and outer membranes of two adjacent mitochondria with high electron density).

This arrangement of mitochondria into several regional subnetworks as opposed to a single, cell-wide network limits the spread of localized mitochondrial dysfunction to within defined volumes.

In both cardiac and Skeletal muscle subnetworks, a rapid electrical and physical separation of malfunctioning (depolarised) mitochondria occurs, consistent with detachment of IMJs, allowing the remaining mitochondria to resume normal function within seconds. This limits the impact of mitochondrial dysfunction.

These rapid alterations in mitochondrial connectivity allow muscle cells to respond to local dysfunction and restore the energy distribution systems to the remainder of the cell.

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