Extraordinary gene transfer between cells observed(malaghan.org.nz)
malaghan.org.nz
Extraordinary gene transfer between cells observed
http://www.malaghan.org.nz/news-and-events/extraordinary-gene-transfer-between-cells-observed/
3 comments
The paper isn't open access, unfortunately [1]. As I recall stem cells have been shown to do this as well, a few years back, so there are probably a couple of other papers out there on the same topic. Interestingly the example I was thinking of was retracted, however. [2]
Nonetheless, university publicity people are very quick to claim "first" and you should always be skeptical about that part of news releases.
There are demonstrations to show that cells will import free-roaming mitochondria. If you put cells and mitochondria into a culture, the cells will pull them in and use them [3]. Researchers have manipulated this mechanism to some degree to obtain the import of specific mitochondria. [4]
So I think there has been the sense that it was expected for at least some cells to be moving mitochondria around between one another under at least some circumstances.
Some further commentary:
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Mitochondria are the powerplants of the cell, more or less. There is a herd of mitochondria in every cell, dividing like bacteria as necessary to keep up their own numbers. Their most important - but by no means only - activity is the generation of adenosine triphosphate (ATP) molecules used as chemical energy stores to power cellular processes. Mitochondria have their own DNA separate from that in the cell nucleus, and it encodes a few vital pieces of protein machinery used in the process of generating ATP. Unfortunately this DNA often becomes damaged in ways that evade cellular quality control mechanisms and lead to a takeover of the cell by malfunctioning mitochondria. The details of this takeover are still under investigation: researchers never see it happening, only the before and after state, which suggests that it is fairly rapid at least. Cells in this dysfunctional state are thought to contribute to a range of age-related conditions by exporting a flood of reactive molecules and damaged proteins into surrounding tissues.
One of the challenges in studying the progression of mitochondrial damage is that mitochondrial dynamics are highly complex. Mitochondria are like bacteria in that they multiply by division, copying their DNA and assembling new ATP-creation machinery in the process. Equally they are also like other cell components in that various complicated processes monitor them and destroy them when they show signs of wear. Further, they can also fuse together, and any two individual mitochondria can contain more than one copy of the mitochondrial genome and differing amounts of molecular machinery. To make matters even more entertaining individual mitochondria promiscuously swap components of that molecular machinery between one another. So you can probably see that it is not exactly straightforward to track the process by which a few thousand of these entities in one cell move rapidly from a state in which one mitochondrion has damaged DNA to that same DNA damage being present in all of the mitochondria. There are dozens of distinct mechanisms at work, few of which are fully understood at this time, and all of which have their own particular constraints and reactions to circumstances.
As is the case for many areas in aging, however, researchers could skip over all of this complexity and bypass full understanding in order to sprint down a more direct path towards treatments. The SENS approach to work on rejuvenation treatments, for example, picks out provision of proteins encoded in mitochondrial DNA as the key point. Provided that those proteins are supplied, it doesn't matter what happens to the mitochondrial DNA, as the necessary machinery is still there. The mitochondria will continue to function correctly rather than malfunction. On that basis there are a number of ways to go: deliver replacement mitochondrial genomes while clearing out existing genomes, put copies of mitochondrial genes into the cell nucleus (plus solve the thorny problem of how to transport the proteins produced back into the mitochondria), deliver RNA that will manufacture proteins at the mitochondria, and so forth. None of these methods requires a full understanding of how mitochondrial damage progresses in order to be effective, but as is usually the case in these matters none of them are well funded in comparison to efforts to generate the full understanding of mitochondrial dynamics. Science as practiced is very much biased towards the generation of understanding first and foremost, which sometimes leaves practical paths towards treatments lost and languishing.
In any case, back to the complexity of mitochondrial dynamics: there is yet another level to all of this that has come under investigation in recent years, which is that cells can under some circumstances exchange components such as mitochondria.
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[1]: http://dx.doi.org/10.1016/j.cmet.2014.12.003
[2]: http://impactaging.com/papers/v3/n6/full/100341.html
[3]: http://dx.doi.org/10.1016/j.transproceed.2013.11.133
[4]: http://onlinelibrary.wiley.com/doi/10.1111/jcmm.12316/full
Nonetheless, university publicity people are very quick to claim "first" and you should always be skeptical about that part of news releases.
There are demonstrations to show that cells will import free-roaming mitochondria. If you put cells and mitochondria into a culture, the cells will pull them in and use them [3]. Researchers have manipulated this mechanism to some degree to obtain the import of specific mitochondria. [4]
So I think there has been the sense that it was expected for at least some cells to be moving mitochondria around between one another under at least some circumstances.
Some further commentary:
-------
Mitochondria are the powerplants of the cell, more or less. There is a herd of mitochondria in every cell, dividing like bacteria as necessary to keep up their own numbers. Their most important - but by no means only - activity is the generation of adenosine triphosphate (ATP) molecules used as chemical energy stores to power cellular processes. Mitochondria have their own DNA separate from that in the cell nucleus, and it encodes a few vital pieces of protein machinery used in the process of generating ATP. Unfortunately this DNA often becomes damaged in ways that evade cellular quality control mechanisms and lead to a takeover of the cell by malfunctioning mitochondria. The details of this takeover are still under investigation: researchers never see it happening, only the before and after state, which suggests that it is fairly rapid at least. Cells in this dysfunctional state are thought to contribute to a range of age-related conditions by exporting a flood of reactive molecules and damaged proteins into surrounding tissues.
One of the challenges in studying the progression of mitochondrial damage is that mitochondrial dynamics are highly complex. Mitochondria are like bacteria in that they multiply by division, copying their DNA and assembling new ATP-creation machinery in the process. Equally they are also like other cell components in that various complicated processes monitor them and destroy them when they show signs of wear. Further, they can also fuse together, and any two individual mitochondria can contain more than one copy of the mitochondrial genome and differing amounts of molecular machinery. To make matters even more entertaining individual mitochondria promiscuously swap components of that molecular machinery between one another. So you can probably see that it is not exactly straightforward to track the process by which a few thousand of these entities in one cell move rapidly from a state in which one mitochondrion has damaged DNA to that same DNA damage being present in all of the mitochondria. There are dozens of distinct mechanisms at work, few of which are fully understood at this time, and all of which have their own particular constraints and reactions to circumstances.
As is the case for many areas in aging, however, researchers could skip over all of this complexity and bypass full understanding in order to sprint down a more direct path towards treatments. The SENS approach to work on rejuvenation treatments, for example, picks out provision of proteins encoded in mitochondrial DNA as the key point. Provided that those proteins are supplied, it doesn't matter what happens to the mitochondrial DNA, as the necessary machinery is still there. The mitochondria will continue to function correctly rather than malfunction. On that basis there are a number of ways to go: deliver replacement mitochondrial genomes while clearing out existing genomes, put copies of mitochondrial genes into the cell nucleus (plus solve the thorny problem of how to transport the proteins produced back into the mitochondria), deliver RNA that will manufacture proteins at the mitochondria, and so forth. None of these methods requires a full understanding of how mitochondrial damage progresses in order to be effective, but as is usually the case in these matters none of them are well funded in comparison to efforts to generate the full understanding of mitochondrial dynamics. Science as practiced is very much biased towards the generation of understanding first and foremost, which sometimes leaves practical paths towards treatments lost and languishing.
In any case, back to the complexity of mitochondrial dynamics: there is yet another level to all of this that has come under investigation in recent years, which is that cells can under some circumstances exchange components such as mitochondria.
-------
[1]: http://dx.doi.org/10.1016/j.cmet.2014.12.003
[2]: http://impactaging.com/papers/v3/n6/full/100341.html
[3]: http://dx.doi.org/10.1016/j.transproceed.2013.11.133
[4]: http://onlinelibrary.wiley.com/doi/10.1111/jcmm.12316/full
Thanks for all the information. So how do you suppose immortal germ line cells deal with mitochondria damage?
It is becoming more and more established that human cells are not really alive. They just are a cooperative of things that are alive. Mitochondria, for instance, are alive. Our cells cannot survive without mitochondria, yet mitochondria can live an thrive without human cells. In a way eukaryot cells are like companies, as opposed to individuals : they're a collection of cooperative agreements between various parties. If you're pedantic eukaryot cells are fictional, like companies : there are no cells/companies, there are only cooperating smaller components that (in theory) could decide to dissolve at any time. But when walking around in the world you could easily be forgiven for thinking they do exist, as they are present, you can interact with them, they often look like they have coherent reactions (even though they don't), there's a wall around them, ...
The article specifies how they deal with mitochondrial damage : the same way a company would deal with a "defective" employee : have security escort them out of the building. Well a cell does what I often think companies would like to do : kill them first, then escort them out of the building, then find a new one (usually by asking an existing one to reproduce, but it seems there are other ways). It's even more similar than you'd think. A eukaryot cell doesn't kill the mitochondria "itself", it asks the golgi apparatus to do it for it (form a lysosome around it).
This research is groundbreaking because it shows our cells behave like companies do in another way : every now and again, they try to replace even perfectly functional employees with better ones.
The article specifies how they deal with mitochondrial damage : the same way a company would deal with a "defective" employee : have security escort them out of the building. Well a cell does what I often think companies would like to do : kill them first, then escort them out of the building, then find a new one (usually by asking an existing one to reproduce, but it seems there are other ways). It's even more similar than you'd think. A eukaryot cell doesn't kill the mitochondria "itself", it asks the golgi apparatus to do it for it (form a lysosome around it).
This research is groundbreaking because it shows our cells behave like companies do in another way : every now and again, they try to replace even perfectly functional employees with better ones.
Thanks. That's a really interesting analogy.
I guess my question is why mitochondria damage Leeds to aging in normal cells but germ line cells must have some way to deal with it flawlessly.
I guess my question is why mitochondria damage Leeds to aging in normal cells but germ line cells must have some way to deal with it flawlessly.
Just for fun, I'm going to post this on creationist forums and see what pretzels they twist their heads into about it.