In a new study published Monday in The Journal of Cell Biology,
researchers from Thomas Jefferson University say such muscle weakness
has long been a common symptom of alcoholics and people with
mitochondrial disease and now they know why.
As the body ages,
cellular organelles called mitochondria self-repair damage by fusing
with other mitochondria and exchanging contents.
Yet that mitochondrial repair process breaks down within
the cells of someone who’s abused alcohol for years, says Gyorgy
Hajnoczky, a pathologist who directs the hospital’s MitoCare Center.
Researchers had previously questioned whether mitochondria
in skeletal muscle used fusion to repair themselves, given the density
of those organelles packed tightly among fibers of muscle cell —
something some saw as impossible.
In the study, Hajnoczky and his
colleagues demonstrated that mitofusin fusion proteins (Mfn1)
were most important for the task in skeletal muscle tissue cells.
To do
so, they devised a system whereby they tagged the mitochondria of
skeletal muscle in laboratory rats with two different colors, looking
for signs of fusion.
In rats whose mitochondria cells displayed the
color red, the researchers programmed mitochondrial cells, through
genetic engineering, to turn green when hit with a laser.
Surprisingly,
the mitochondria not only fused in those cells but ranged within the
intracellular body much further than previously thought.
Researcher Veronica Eisner said in a press release they’d showed “for the first time that mitochondrial fusion occurs in muscle cells.”
After IDing these Mfn1 proteins, the researchers found that
levels fell by as much as half when tested on laboratory rats
simulating the adult alcoholic.
And as suspected, muscle strength
dropped with attendant losses of the protein used in fusion, the
researchers said.
"That alcohol can have a specific effect on this one gene
involved in mitochondrial fusion suggests that other environmental
factors may also specifically alter mitochondrial fusion and repair,"
Hajnoczky said.
"The work provides more evidence to support the concept
that fission and fusion — or mitochondrial dynamics — may be responsible
for more than just a subset of mitochondrial diseases we know of."
Researchers first suspected mitochondrial fusion as the
problem when investigating Autosomal Dominant Optical Atropy disease and
a specific type of Charcot-Marie-Tooth disease, both of which are
mitochondrial diseases.
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