mitochondrial SWELLING - reversible or irreversible?

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Phloston

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Sources seem to say different things, so I don't have a clear answer here.

As far as I've thought, mitochondrial swelling is reversible but permeability/vacuolization/intra-mitochondrial amorphous density formation is irreversible.

Another thing, is it mere ATP depletion that causes mitochondrial swelling (I believe one of the NBMEs suggested this)?

Part of me wants to think Ca2+ influx into the mitochondria causes a degree of swelling, but that would be irreversible, not reversible, right?

Anyway, does anyone have thoughts on this?

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lol I started to instantly forget things after my test but to my knowledge what you said is correct. Mitochondrial swelling is reversible and permeability causes irreversibility.

lack of ATP causes the Na+/Ca2+ channels and Na+/K+ channels on the plasma membrane to not work (ATP dependent) which causes an accumulation of ions and therefore water to influx and swell the cell.
 
Swelling is the hallmark of reversible damage, whereas membrane damage is hallmark of irreversible damage. As per your second question, I know that not being able to use the Na/K ATPase pump is the cause of cellular swelling. However, don't think it's the same mechanism for mitochondria. According to Goljan, he states salicylate poisoning and alcohol are the causes, but doesn't go into any further details as per the mechanism.

Source: Pathoma
 
Swelling is the hallmark of reversible damage, whereas membrane damage is hallmark of irreversible damage. As per your second question, I know that not being able to use the Na/K ATPase pump is the cause of cellular swelling. However, don't think it's the same mechanism for mitochondria. According to Goljan, he states salicylate poisoning and alcohol are the causes, but doesn't go into any further details as per the mechanism.

Source: Pathoma

Going through Goljan he states that salicylates and poisoning are mitochondrial toxins, so it would be mitochondrial membrane damage which is irreversible. This was in the uncoupler protein section in a blue box.

I think the swelling is related to the protein channels on the inner mitochondrial membrane, does anyone know if these utilize ATP?
 
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Mitochondrial bioenergetic research shows that mito membrane damage is not completely irreversible. Remember the mitochondrial are in there own life cycle separate from the cell cycle.

The mito life cycle is composed of mitochondrial fusion and fission to regenerate the membrane potential. There are many mitochondrial outer & inner proteins in play during this mitochondrial life cycle. The main outer membrane proteins are MFN2/MFN1 (mitofusion). The main inner protein involved involved in mito fusion is OPA1 (optic atrophy 1), which is a GTPase. It is known that when mito are stressed (many reasons) they tend to change in morphology towards the swollen characteristic. They tend to get stuck in the fusion position with the OPA1 protein being over-expressed.
 
lol I started to instantly forget things after my test but to my knowledge what you said is correct. Mitochondrial swelling is reversible and permeability causes irreversibility.

lack of ATP causes the Na+/Ca2+ channels and Na+/K+ channels on the plasma membrane to not work (ATP dependent) which causes an accumulation of ions and therefore water to influx and swell the cell.

Agree. I believe mito swelling is reversible. I've studied mito morphology dynamically via confocal microscopy and I promise in response to mild stress (uncouplers, calcium overload via ionophores) they do in fact swell, and become somewhat punctate (although like another poster said, they generally get stuck in a fusion-type morphology. I was actually able to prove a downregulation a fission protein in response to calcium overload (in nerve cells at least).

Overtime, they do however recover, and assume their normal morphology.

Also, from what I remember, mito protein import is both ATP dependent and independent... so if I had to choose one, I'd say it's probably ATP dependent.


YESSS finally something useful I can do with my Msc... haha
 
Our syllabus reads:

"With severe injury cytosolic calcium may be increased causing activation of
endonucleases, phospholipases and other enzymes. This may represent the ultimate
cause of cell death (the irreversible last step)."
 
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