Sunday, April 27, 2014

How Alcoholism Causes Muscle Weakness

It’s a mitochondrial thing.

Chronic alcohol intake weakens muscles. This condition can take the form of numbness or shooting pains in arms and legs, muscle cramps, fatigue, heat intolerance, and problems urinating. In some cases it can lead to diarrhea, nausea, vomiting, spasms, muscle atrophy, and movement disorders, even chronic pain and long-term disability. Leg symptoms are the most common. Alcohol-related neuropathy of this kind generally develops over time and gradually worsens. But until recently, the mechanism behind alcoholic neuropathy has remained obscure.

As it turns out, it’s a mitochondrial thing. Mitochondria, as we all remember from 10th grade biology, are little structures known as the “power plants” of cells. They are constantly changing tubular organelles that form networks inside of cells to convert oxygen into energy used in cellular processes. But if the proper enzymes that trigger the process go missing, less energy gets produced for activities like muscle function.

Patients with certain forms of mitochondrial disease, in which mitochondria fail to self-repair, show pronounced muscle weakness as a symptom. In some cases, this is due to a mutation for a particular mitochondrial fusion protein, leading to “late onset myopathy.”

Muscle tissue repairs itself through a process known as mitochondrial fusion, through which a broken mitochondrial cell component can repair itself by fusing with healthy mitochondria and exchanging bodily fluids, so to speak. It had previously been thought that the tightly packed fibers of muscle cells might not allow for normal fusion among the mitochondrial organelles found in skeletal muscle. Not so, according to a recent paper for the Journal of Cell Biology. Principle author Gyorgy Hajnoczky in the Department of Pathology, Anatomy and Cell Biology at Philadelphia’s Thomas Jefferson University writes that the animal study shows how chronic alcohol exposure “suppresses mitochondrial fusion in muscle fibers.” The problem worsens over time due to “lesser metabolic fitness of the mitochondria, which progressively hinders calcium cycling during trains of stimulation.” What this means is that, in cases of prolonged heavy drinking, mitochondria have less “reserve capacity” for supporting calcium regulation in cells.

The researchers began with the known finding that “mitochondrial ultrastructure damage is apparent in the skeletal muscle of alcoholics, and mitochondria and their quality control are considered to be a primary target of chronic alcohol exposure.” Furthermore, “mitochondria represent a major target of alcohol and loose their normal shape upon persistent alcohol exposure.”

The study, funded by the NIAAA, demonstrated that mitochondrial fusion is the key to repair in skeletal muscle, as it is in other muscle tissue. In the study, researchers color-tagged mitochondria in the skeletal muscle of rats, and demonstrated that mitochondrial fusion occurs, and is governed by key players called mitofusin 1 fusion proteins (Mfn1). Chronic alcohol abuse interferes with this repair process. In the study, alcoholic rats showed a decrease in Mfn1 levels of up to 50 percent, while other fusion proteins were not affected.

“That alcohol can have a specific effect on this one gene involved in mitochondrial fusion suggests that other environmental factors may also alter specifically mitochondrial fusion and repair,” Hajnoczky said in a prepared statement.

The study has provided insight “into why chronic heavy drinking often saps muscle strength,” which could also “lead to new targets for medication development,” according to Dr. George Koob, head of the National Institute on Alcohol Abuse and Alcoholism (NIAAA).

Eisner V., Lenaers G. & Hajnoczky G.  Mitochondrial fusion is frequent in skeletal muscle and supports excitation-contraction coupling, The Journal of Cell Biology,    DOI:

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Unknown said...

I saw the press release about this and I'm so glad you wrote about it. Well done!

Ernie said...

Interesting stuff..but not that surprising when you think about it.

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