Brian Glancy, Lisa
M. Hartnell, Christian A. Combs, Armel Femnou, Junhui Sun, Elizabeth
Murphy,
Sriram Subramaniam
and Robert S. Balaban.
THE
DRAWBACK OF THE MITOCHONDRIAL NETWORK
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.
EXISTENCE
OF SUBNETWORKS
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).
PROTECTIVE
FUNCTION OF THE SUBNETWORKS
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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