Mitochondrial dysfunction - influence on TRPA1

In my last blogposts I have brought links to many articles informing that the ion channel Transient Receptor Potential Ankyrin 1 (TRPA1) is affected in a number of diseases/conditions, which has relation to Myalgisk encephalomyeltitis (ME). This is Multiple Chemical Sensitivity (MCS), inflammation, pain (fibromyalgia), autonomic dysfunction, Irritable Bowel Syndrome (IBS), bladder pain syndrome and neuropathy.

TRPA1 and the ion channel Transient Receptor Potential Vanilloid 1 (TRPV1) are also involved in a condition called exercise-induced anaphylaxis. And something is wrong about exercise and ME. Is there a shared biochemistry?

Thus, it is reasonable to suspect TRPA1 is affected in ME.

For many years researchers have looked at the relationship between ME and mitochondrial dysfunction. It is an obvious idea to see how TRPA1 and TRPV1are affected by mitochondrial dysfunction.

There is growing evidence that the mitochondrial dysfunction contributes to the complex mechanism of many diseases. Increased formation of Reactive Oxygen Species (ROS) are suspected to contribute to the chronic inflammatory condition in many diseases such as Type II diabetes, cardiovascular disease, and neuroinflammation. And we already know ROS are elevated in ME.

Mitochondrias and TRPA1 are found in peripheral terminals of sensory nerves. A group of researchers wanted to investigate how ROS from mitochondrial dysfunction could affect TRPA1 (and TRPV1). For this experiment they used "bronchopulmonary C fibers" (the nerve fiber, which is connected to the lungs) from mice.

The experimental description can be read by the article mentioned below. I am just quoting the exciting conclusion:
" In conclusion, we present evidence that acute mitochondrial dysfunction activates airway sensory nerves preferentially via TRPA1 through the actions of mitochondrially-derived ROS. This represents a novel mechanism by which inflammation may be transduced into nociceptive electrical signaling."

Now, we know that TRPA1 and mitochondrial dysfunction are linked together. Can we use this knowledge in the research into ME and co-morbid conditions?

Sensory Nerve Terminal Mitochondrial Dysfunction Activates Airway Sensory Nerves Via Transient Receptor Potential (TRP) Channels
http://www.ncbi.nlm.nih.gov/pubmed/23444014

More knowledge about TRPA1:
Chapter 11 TRPA1 : A Sensory Channel of Many Talents
http://www.ncbi.nlm.nih.gov/books/NBK5237/

In Danish - på dansk:

Mitokondrie dysfunktions påvirkning af TRPA1
I de seneste blogindlæg har jeg bragt links til en lang række artikler, der viser at ion kanalen Transient Receptor Potential Ankyrin 1 (TRPA1) er påvirket i en lang række sygdomme/tilstande, som har relation til Myalgic encephalomyeltitis (ME). Det drejer sig om Multiple Chemical Sensitivity (MCS), inflammation, smerte (fibromyalgi), autonom dysfunktion, Irritable Bowel Syndrome (IBS), kronisk smertefuldt blæresyndrom og neuropati.

TRPA1 er også sammen med ion kanalen Transient Receptor Potential Vanilloid 1 (TRPV1) involveret i en tilstand kaldet motionsinduceret anafylaksi. Og der noget galt med motion og ME. Så mon ikke der kunne være noget overlappende biokemi for disse tilstande?

Der er således begrundet mistanke til at kigge nærmere på, om der kan opstilles en hypotese om TRPA1 er påvirket i ME.

Igennem mange år har forskere set på sammenhæng mellem ME og mitokondrie dysfunktion. Det er derfor en nærliggende tanke at om TRPA1 og TRPV1 påvirkes af mitokondrie dysfunktion.

Der er en voksende bevismængde, der viser at mitokondrie dysfunktion bidrager til den komplekse mekanisme i mange sygdomme. Øget dannelse af Reactive Oxygen Species (ROS) er mistænkt for at bidrage til den kroniske inflammatoriske tilstand i mange sygdomme som f. eks. type II diabetes, kardiovaskulær sygdom og neuroinflammation. Og vi ved allerede, at ROS er forhøjet hos ME patienter.

Mitokondrier og TRPA1 findes i perifere terminaler af sensoriske nerver. En gruppe forskere ønskede at undersøge, hvordan ROS fra mitokondrie dysfunktion kunne påvirke TRPA1 (og TRPV1). Til forsøget anvendte de ”bronchopulmonary C-fibres” (nervefiber, der har forbindelse til lungerne) fra mus.

Selve forsøgsbeskrivelsen kan læses af nedennævnte artikel. Jeg vil blot opridse den spændende konklusion:

”Det kan konkluderes, at vi fremviser evidens for, at akut mitokondrie dysfunktion aktiverer luftvejenes sensoriske nerver fortrinsvis via TRPA1 igennem virkningen af mitokondrie- afledt ROS. Dette repræsenterer en ny mekanisme ved hvilken inflammation kan omformes til nociceptiv elektrisk signalering.”

Nu ved vi altså, at TRPA1 og mitokondrie dysfunktion hænger sammen. Kan vi udnytte denne viden i forskning i ME og ko-morbide tilstande? 

Reference:
Sensory Nerve Terminal Mitochondrial Dysfunction Activates Airway Sensory Nerves Via Transient Receptor Potential (TRP) Channels
http://www.ncbi.nlm.nih.gov/pubmed/23444014

Og mere viden om TRPA1:
Chapter 11 TRPA1 : A Sensory Channel of Many Talents
http://www.ncbi.nlm.nih.gov/books/NBK5237/

Artikel om mitokondrie sygdomme på dansk
http://www.ugeskriftet.dk/LF/UFL/2003/07/pdf/VP38126.pdf