Mitochondrial Dynamics Triggers Inflammation When Too Imbalanced in Either Direction

Mitochondria are the distance descendants of symbiotic bacteria, and the hundreds of mitochondria present in every cell behave much like bacteria. They constantly fuse together, undergo fission, and swap component parts. This mitochondrial dynamics becomes imbalanced in aged tissues, the immediate consequence of epigenetic changes that alter the availability of various proteins involved in fusion or fission. Researchers here note that pushing mitochondrial dynamics too far in either direction, too much fusion or too much fission, will produce inflammatory signaling. This is an interesting connection between mitochondrial dysfunction and the chronic inflammation characteristic of aging.

Mitochondrial dynamics regulate mitochondrial homeostasis through the modulation of multiple elements such as organelle interaction and mitochondrial morphology. In this study, we provide evidence that mitochondrial dynamics also controls the activation of intracellular inflammatory pathways. Our conclusion is based on a number of observations, namely that: a) repression of the mitochondrial fusion proteins Mfn1 or Mfn2 induces mitochondrial fragmentation and TLR9-dependent NFκB activation; and b) Drp1 or Fis1 repression causes mitochondrial elongation and both NFκB-dependent and type I IFN inflammatory responses.

Given the role of mitochondrial dynamics in regulating mitochondrial function and mitophagy, it is conceivable that alterations in these processes could be involved in triggering inflammation upon mitochondrial dynamics disturbances. Here, we show that indeed, the different manipulations induced by repressing Mfn1, Mfn2, Drp1, or Fis1 lead to very different patterns of alterations in mitochondrial membrane potential, mitochondrial superoxide production, mitochondrial mass, mitochondrial respiration, or mitophagy, which does not explain the inflammatory response observed in each condition. In contrast, we find that the inflammatory responses depend on the presence of mitochondrial DNA (mtDNA), which suggests that those changes in mitochondrial function and quality are consequences of adaptations in mitochondrial biology that are not directly related to the inflammatory response.

Mitochondrial stress can trigger sterile inflammation by inducing mtDNA mislocation and allowing mtDNA recognition by DNA sensors, mitochondrial dynamics are essential in maintaining mitochondrial homeostasis, and muscle inflammation and atrophy are hallmarks of impaired muscle health. Based on our findings, we propose that the maintenance of mitochondrial dynamics is a key factor in preventing the trigger of inflammatory responses characterized by mtDNA mislocation and DNA sensor activation, and that muscle inflammation induced by mitochondrial fragmentation plays a causative role in the development of muscle atrophy.



...and if the people concerned about this cared about any of us, there would be an exercise study driven by this. Fact: Resistance training, and a diet to optimize it, alters the mitochondrial size and population, and perhaps efficiency in muscles. If that is the case, than we have the means to control some of the factors looked at in this study in our own bodies. Why can't there be a market for simple blood or urine tests that measure inflammation? The ", we propose" at the end of this article should be immediately followed up with a brain storming session on how to get on with it.

Posted by: Thomas Schaefer at January 25th, 2023 8:44 AM

How does one restore balance? Only possibilities I've found in this country are exercise, light therapy, and maybe urtholin A

Posted by: august33 at January 25th, 2023 4:03 PM

Would heat shock protein also help?

Posted by: STAN Kanarowski at January 29th, 2023 7:48 PM
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