So after a brief review of mitochondrial dynamics of fusion and fission, here are some thoughts:
* Reviewing fusion and fission, what is very very clear is that fusion is absolutely critical to being energetic and healthy. When the key proteins involved in fusion fail, you get a number of very serious diseases, some of which are profiled in the summary article above. The proper function of fusion is critical to peak bioenergetics of the cell, so if you want to oxidize aerobically and efficiently, you must have good fusion.
* Fission is more of a cloud. There is a clear association with autophagy and mitophagy and reduced bioenergetics. One would assume that this mitochondrial state helps to support fasting or starvation, by removing non-optimal structures from the cell. The problem is that the studies showing lifespan extension from autophagy are murky. And I have found at least one study in worms where suppressing autophagy as the worms age EXTENDS LIFESPAN.
I am not saying that it plays out in humans the way it plays out in worms. But I am saying that the science behind autophagy and mitochondrial fission really is not at a level where you can definitively say that fission is good for lifespan extension. By hypothesis only, maybe it ends up being shown that autophagy is a necessary adaptation for a low-energy environment, but that - on net - the absence of high bioenergetics to the cell is far more harmful than the presence of fission during autophagy / mitophagy is good. There is a complex system at work here and we are making a simplistic assumption that because mitophagy does something favorable that entering into the state where it occurs is on net beneficial to our bodies. Maybe yes. Maybe no. The worm study I linked above should make you think twice.
This then feeds into my question posted earlier: even if you want to believe that fission is good for lifespan extension, how much is enough? How much is actually harmful? How long do these cycles need to last to be therapeutic? Do we have studies answering any of those questions in any kind of organism?
Edited by pone11, 12 June 2018 - 09:12 PM.