Sustainability from a cell perspective

Abstract

Sustainability is a worldwide problem, for cells as it is for human beings and our whole planet. The key to solving the sustainability problem is recycling. In cells, this is accomplished within the lysosome. All biological macromolecules, such as proteins and nucleic acids, which are past their use-by-date, are transported into the lysosome, where enzymes degrade them into their monomeric building blocks. These enzymes are only active at the low pH of ~4.7 of the lysosome lumen. After degradation, the building blocks are transported out of the lysosome into the cytoplasm, where they are used for the biosynthesis of new proteins and nucleic acids. Because of the need to encapsulate the degrading enzymes within the lysosome to avoid damage to functionally active proteins and nucleic acids, the lysosome membrane is a powerhouse of solute transport within the cell. This recycling process is crucial for the survival of cells, particularly neurons, which are no longer capable of cell division. Defects in this process cause many hereditary neurodegenerative diseases. But because of their rarity, pharmaceutical companies are not particularly interested in finding cures. However, the diagnosis of neurodegenerative disease is devastating for the family of any afflicted child. One group of neurodegenerative diseases is termed Batten disease. While symptoms vary, all are caused by lysosomal dysfunction, resulting in the steady build-up of waste material in the cell. Disease progression is typically characterised by the development of blindness, followed by the onset of seizures and early death, typically in the twenties. Understanding the disease would not only help its sufferers but also provide valuable information on a crucial cell function, i.e. how cells recycle their waste. We will describe how biophysical measurements are helping to provide some insights into the molecular physiology of lysosome function and the pathology of Batten disease.