New Insight into the Cell’s Quality-Control Systems Provided Added Evidence for Design
It’s easy to take garbage men for granted—until they go on strike or can’t do their job properly, which is the case in Naples, Italy.
Getting rid of trash is essential for well-run households, businesses, and communities. Piles of waste are an unpleasant health hazard.
Disposing of garbage is just as necessary for cells as it is for municipalities. Cells have to get rid of their molecular debris and waste to function properly. In most cases, the cell is able to remove its biomolecular rubbish. But in some cases, it can’t. The consequences can be devastating. Accumulating piles of biochemical waste are a health hazard for cells too. As a case in point, some neurodegenerative diseases, like Huntington’s, involve the build-up of biochemical waste in the form of protein aggregates.
Understandably, biologists are interested in trying to learn how and why protein waste accumulates in cells and what can be done to eliminate it. New work by Stanford University scientists published in Nature provides important insight into how protein waste is processed by the cell. This new knowledge suggests a possible strategy to help cells clear out intractable biomolecular garbage. This new understanding also adds to the evidence that life stems from a Creator’s hand.
Last week I described the make-up of the cell’s garbage and the central cogs in the cell’s waste-disposal machinery. This week I’ll describe the new research by the team of cell biologists from Stanford University and discuss its implications.
Protein Waste Disposal
Much of the cellular rubbish consists of protein aggregates. Proteins are chain-like molecules that fold into precise three-dimensional structures. A protein’s three-dimensional architecture determines its function. Proteins play a key role in virtually every cellular function and help form nearly every cellular structure.
Cells constantly make and destroy proteins. Specialized proteins used in particular activities are manufactured only when needed. Once these proteins have outlived their usefulness, the cell breaks them down into their constitutive amino acids. However, proteins that play a central role in the cell’s operation are produced on a continual basis. These proteins inevitably suffer damage from use and must be destroyed and replaced with newly made proteins. Faulty manufacturing also produces protein waste. The folding of newly made protein chains into their native three-dimensional architecture is error-prone. Misfolded proteins must be removed because they tend to form aggregates inside the cell.
Damaged or misfolded proteins are tagged with a small protein molecule called ubiquitin. These molecular tags inform the cell’s machinery that the damaged protein needs to be destroyed. A massive protein complex called a proteasome demolishes damaged, ubiquitinated proteins.
Accumulation of Protein Waste and Quality Control
Most unneeded, damaged, and misfolded proteins are readily cleared by the cell’s protein degradation system. However, some are not. These problematic proteins interact with each other to form large insoluble aggregates inside the cell. Most biologists think the failure of the cell’s machinery to eliminate these aggregated proteins stems from faulty quality-control operations in the cell.
As I describe in The Cell’s Design, every key stage, including the final step, of protein production is accompanied by quality-control checkpoints. These include the final step in the process. The proteasome eliminates any faulty proteins. The placement of these quality-assurance checkpoints occurs at strategic stages in the production process in a way that ensures reliable protein production while generating manufacturing efficiency.
In The Cell’s Design, I assert that biochemical quality assurance exemplifies the remarkable ingenuity that defines the cell’s chemistry and reinforces the conclusion that life has a supernatural basis. Effective and efficient quality-control procedures don’t just happen. Rather, they are characterized by intentional foresight. Sound quality-control systems require careful planning, a detailed understanding of the manufacturing process, the product, and the way that the product will be used. All of these features are evident in the quality-control activities in the cell.
Still, the inability to effectively eliminate aggregated proteins undermines the case for biochemical intelligent design if it is due to ineffective quality-control systems. But as new work reveals, the protein degradation process is much more complicated than previously thought.
Two Cellular Locales for Protein Waste Management
Stanford cell biologists performed a series of elegant experiments that revealed two cellular locales for protein waste disposal. The first region is situated near the juncture of the nucleus and the endoplasmic reticulum. This site is rich in proteasomes. Proteins sent to this location are highly ubiquinated and soluble. The proteasomes readily degrade or refold these proteins. (See my article from last week.)
The other site, which is located near the exterior of the cell, consists of insoluble protein deposits. Proteins sent to this location are lightly ubiquinated and insoluble. These proteins form insoluble aggregates that can’t be eliminated by the cell. Over time these deposits accumulate in the cell.
Proteins found in the second site include those associated with the onset of Huntington’s disease. They also includes proteins that would normally be cleared from the cell, but fail to be adequately ubiquinated because of stress. Under stressful conditions, a large number of proteins unfold, overwhelming the protein degradation system. The ageing process also contributes to proteins found in this site.
Production of insoluble protein deposits does not appear to be a malfunction of the cell’s quality-control systems. Instead it represents an elegant strategy for managing cellular waste. By piling insoluble protein aggregates into these deposits, the cell’s quality-control operations have effectively sequestered these harmful aggregates from the cell’s machinery, minimizing their harmful effects.
The authors of this study also note that the formation of these deposits provides a means to limit the transmission of insoluble protein aggregates to daughter cells generated from cell division. If distributed throughout the cell, a significant portion of the insoluble protein aggregates would be transferred to both daughter cells every time cell division took place. By incorporating all of the insoluble proteins into a single deposit, only one daughter cell is saddled with these potentially harmful materials. The other daughter cell winds up with a pristine cytoplasm.
Additionally, the Stanford researchers detected markers that flag the insoluble protein aggregates for autophagy). This process involves the breakdown of the cell’s own components by its digestive machinery. Autophagy provides a separate means to clear misfolded proteins from the cell independent from proteasomes.
Based on this new research, the formation of insoluble protein deposits no longer appears to be due to the failure of the cell’s quality-control systems. Instead it reveals that the quality assurance operations in the cell are far more complex and sophisticated than originally thought. The generation of insoluble protein aggregates serves a protective function for the cell and also provides a pathway to eliminate intractable protein conglomerations from inside the cell.
Like garbage in the streets of Naples, the biochemical evidence for intelligent design keeps piling up.
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