Why carbon monoxide gas kills organisms

Thus, CO-induced preconditioning generates an anti-oxidant state, which promotes liver resistance against MMP. The direct role of CO on targeting mitochondria was evaluated in isolated nonsynaptic mitochondria from rat cortex.

In isolated liver mitochondria from mouse, pretreatment with CO also inhibited mitochondrial swelling, depolarization, and the opening of a pore through the inner membrane, in a ROS-dependent manner [ 20 ]. In addition, cytochrome c oxidase transiently responded to low concentrations of CO by decreasing its activity in the first 5 minutes after treatment, while later on there was an increase of COX activity detected up to 30 minutes [ 20 ].

It is worth of note that CO stimulates the antiapoptotic protein Bcl-2 expression in lung and cerebral ischemia models [ 60 , 61 ], and Bcl-2 can translocate into mitochondrial membranes for preventing their permeabilization and cell death. Thus, CO is also capable for preventing MMP by indirectly acting on Bcl-2 expression levels and subcellular localization.

Low concentrations of CO are able to activate distinct endogenous cell defence mechanisms: antiapoptosis, anti-inflammation, antiproliferation, metabolism improvement, cardioprotection, and so forth. By preconditioning the cells CO is a cytoprotective factor, and mitochondria appear as the main cellular targets. In addition, CO is an endogenous gaseoustransmitter, which is physiologically generated in response to several types of stress. Diverse, and apparently controversial, data are available in the literature concerning CO model of action on mitochondria, in particular on cytochrome c oxidase activity and on oxygen consumption.

One can speculate that CO biological activity might depend on two main factors: period of CO exposure and gas concentration, giving rise to distinct responses.

Furthermore, different CO sources increase the system complexity and do not facilitate data comparison. For instance, CO can be applied by different modes: i one single burst of CO CO-saturated solutions fast gas diffusion , ii gas exposition continuously application during the period of exposition , and iii CO-releasing molecules. Depending on the used CORM and its specific molecular characteristics, these molecules can be slow or fast CO releasers or can differently respond to tissues or to a physiological situation, such as an increase on oxidative stress.

In conclusion, CO controls mitochondrial functioning and oxidative metabolism, improving cellular energetic state, by modulation: COX activity, oxygen consumption, mitochondrial biogenesis, and ROS generation Figure 3. Additionally, CO also prevents cell death: i by directly targeting mitochondria and inhibiting mitochondrial membrane permeabilization MMP , ii by increasing antiapoptotic gene expression, such as Bcl-2, which also prevents MMP, or iii by interacting with the apoptosis-inducing cytochrome c-cardiolipin complex and inhibiting caspase activation [ 62 ].

The future in CO research field lays on the disclosure of the cross-talk between cell death and cell metabolism modulation Figure 1. Mitochondria are the key organelle involved in the control of both cellular events. Thus, searching for the physiological mitochondrial target of CO and the biochemical and cellular mechanisms involved is crucial for the development of this gaseoustransmitter as a novel therapeutic agent.

Queiroga et al. This is an open access article distributed under the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Article of the Year Award: Outstanding research contributions of , as selected by our Chief Editors. Read the winning articles. Journal overview. Special Issues. Queiroga, 1,2,3 Ana S. Almeida, 1,2 and Helena L.

Academic Editor: Catherine Brenner. Received 11 Nov Accepted 09 Jan Published 20 Mar Abstract Mitochondria present two key roles on cellular functioning: i cell metabolism, being the main cellular source of energy and ii modulation of cell death, by mitochondrial membrane permeabilization. Introduction Carbon monoxide CO is a colorless and odorless small molecule, widely known as a lethal gas and as a toxic air pollutant. Figure 1. Figure 2. Proposed models for CO action on mitochondria.

The exact mitochondrial target is not fully understood, but complexes II and IV are strong candidates. Figure 3. CO controls mitochondrial functioning and improves cellular energetic state increased ATP generation by two main ways: enhance of oxidative phosphorylation and induction of mitochondrial biogenesis. References C. View at: Google Scholar R. Coburn, W.

Blakemore, and R. View at: Google Scholar D. Slebos, S. Ryter, and A. Tenhunen, H. Marver, and R. View at: Google Scholar S. Ryter, J. Alam, and A. Motterlini and L. Soares and F. Bannenberg and H. Boczkowski, J. Poderoso, and R. Roberts, H. Youn, and R. Greenberg, K. Jin, and A. Nienhaus and G. Cooper and G. Chance, M. Erecinska, and M. Brown and C. View at: Google Scholar J. Alonso, F. Cardellach, S. Zuckerbraun, B.

Chin, M. Bilban et al. Queiroga, A. Almeida, C. Martel, C. Chronic exposure to carbon monoxide can have extremely serious long-term effects, depending on the extent of poisoning. The section of the brain known as the hippocampus is responsible for the formation of new memories and is particularly susceptible to damage. These effects do not always present themselves immediately and can occur several weeks or more after exposure.

Whilst the majority of people suffering from long-term effects of carbon monoxide poisoning recover with time, some people suffer permanent effects, particularly when it comes to organ and brain damage. If you are exposed to carbon monoxide over a long period of time, you can still be poisoned, even if the level of concentration is very low.

Lesser concentrations of 20 or 30 PPM parts per million can still be harmful if you are exposed for several hours. It is not known whether low levels of exposure can cause permanent brain damage, however, they are likely to cause persistent headaches, memory loss, depression, light-headedness, nausea and vomiting.

The respiratory system struggles to distribute air around the body because carbon monoxide deprives the blood cells of oxygen. This results in shortness of breath, particularly when undertaking strenuous activities.

Every-day physical and sporting activities will take more effort and leave you feeling more exhausted than usual. These effects can worsen over time as your body's power to obtain oxygen becomes increasingly compromised.

Both your heart and lungs are put under pressure as the levels of carbon monoxide increase in the body tissues. If no active bacteria is present, the CO dissipates. But if dangerous microbes are lurking, the CO takes on a new responsibility and attaches itself to specific locations on the bacteria.

And this, he explains, serves as the second signal to alert the immune cells to take action. The discovery unveils a new concept and offers a new avenue for the development of therapies to complement or potentially reduce the need for antibiotics and thus limit the development of antibiotic resistance, say the authors. From a clinical perspective, one could envision CO being administered to patients with ongoing infections to help reduce the risk of dangerous complications, such as sepsis, SIRS and, ultimately, multi-organ failure.

Our hope is that we will be able to test these applications in clinical trials and provide the body with a new weapon of mass destruction -- one the host employs against invading armies of bacteria. Note: Content may be edited for style and length. Science News. Lee, Brian S. Zuckerbraun, Richard Flavell, Miguel P. Have your heating system serviced annually. Quick Links.

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