Ouroboros on Leaky Cellular Pores
Some small but important collections of cells in our body are as old as we are - they are never replaced. So for those cells, we should be interested in what happens to them as they grow old with us. Here, Ouroboros looks at a recently uncovered phenomenon: "How do cells get rid of their garbage? ... slowly dividing or postmitotic cells must activate degradative pathways [e.g. autophagy] in order to prevent accumulation of potentially toxic damaged macromolecules and dysfunctional organelles. ... As an example, let’s consider the nuclear pore complex (NPC): it's [huge, complex, and topologically challenging] (the pore crosses the nuclear envelope and creates a hole in the process). Many NPC components aren't in dynamic equilibrium with cytosolic pools, so if we want to turn over any of these proteins we would have to somehow take out the entire NPC, repair the ensuing damage to the membrane, and then either re-insert the NPC (which I don't believe actually happens) or synthesize a new NPC to restore the lost import/export capacity. Unfortunately, new nuclear pores are probably only created during [mitosis as a part of cell division] .... So how do postmitotic cells turn over and degrade NPCs? The answer [is] that they probably don't. Instead, NPCs get old, and accumulate damage, and eventually stop doing their job."