Cells operate according to their genetic programming, each cell having its own specialization. Cells can also correct themselves if their genetic programming goes awry: they perform an internal act of self-destruction, by “self-eating” or degrading unwanted segments or components of their innards in a process known as autophagy. This was thought to only happen outside of the nucleus of the cell, but a new study in Nature shows it happening within the nucleus, where our DNA is held. This could have important implications: autophagy within the nucleus appears to play a role in protecting the body against the onset of cancer.
The researchers of this study directly observed the act of macroautophagy, a subset of autophagy that involves the eradication of damaged cell components (organelles) and unused proteins. A spherical membrane structure known as the autophagosome is used to as a sort of garbage truck, taking the damaged component to a region of the cell called the lysosome. Here, specialized acidic compounds are used to chemically degrade the component.
These controlled destructive processes within the cell nucleus had not been previously observed. This study shows for the first time the macroautophagy of nuclear material within mammalian cells; specifically, damaged sections of a network of protein filaments within the membrane of the cell nucleus.
This protein network – the nuclear lamina – provides mechanical support to the nucleus. A previous study revealed that the breakdown of the lamina was accompanied by a protrusion of nuclear material into the outer layers of the cell. Among other things, a key protein (LC3), a lamina segment (laminB1) and protein/DNA complexes (chromatin) were found within this protrusion. The team found that these three components are ejected from the nucleus into the outer cell and tagged for destruction in response to cellular stress that can cause cancer.
Cancer is essentially the uncontrolled division and proliferation of cells within the body. It starts when a cell’s DNA is damaged, or a gene prone to becoming cancerous is activated. By initiating the digestion of the lamina cancer can be stopped before it even starts.
“The nucleus is the headquarters of a cell,” lead author Zhixun Dou said in a statement. “When a cell receives a danger alarm, amazingly, it deliberately messes up its headquarters. Our study suggests this new function of autophagy is a guarding mechanism that protects cells from becoming cancerous.”
The regular destruction of the lamina also promotes senescence, the biological aging process. The researchers found that late middle-aged normal cells lived 60% longer if they blocked the breakdown of the lamina; the age extension is equivalent to a 70-year-old person living to over 110 years old.
Blocking this protection mechanism comes at a price, though: without the senescence mechanism there is no autophagy-driven process to destroy cancer-prone cellular material. Cells can only protect you from cancer if they are allowed to age normally, it seems.