A fault with the waste removal system that helps to keep our brain cell mitochondria healthy may play a role in neurodegenerative disease, a new study led by researchers at the University of Nottingham has found.
Dr Lynn Bedford, in the University’s School of Life Sciences, said:
“The study highlights the importance of the ubiquitin proteasome system (UPS) for healthy mitochondria. The UPS is like a waste disposal system that removes small unwanted proteins from inside cells. If waste is not removed it will build up over time and become toxic, causing cells to go wrong and eventually die."
Ubiquitin Proteasome System Faults
Irregularities in the UPS may contribute to neurodegenerative diseases such as Parkinson’s and Alzheimer’s because they are caused by the death of neurons – the network through which we transfer information in our brain.
Using gene targeting in mice, the researchers have discovered that a faulty UPS in neurons leads to damaged mitochondria that produce less energy. Damage to mitochondria is also known to produce harmful molecules that injure the cell, known as oxidative stress, so it is vital that the brain is able to keep mending, removing and replacing them.
The study also found that when the ubiquitin proteasome system was faulty, the damaged mitochondria were not removed from neurons in the normal way by the process of autophagy, the disposal system that breaks down larger parts in the cell like mitochondria.
Aslihan Ugun-Klusek, Michael H Tatham, Jamal Elkharaz, Dumitru Constantin-Teodosiu, Karen Lawler, Hala Mohamed, Simon M L Paine, Glen Anderson, R John Mayer, James Lowe, E Ellen Billett, Lynn Bedford Continued 26S proteasome dysfunction in mouse brain cortical neurons impairs autophagy and the Keap1-Nrf2 oxidative defence pathway Cell Death and Disease, 2017; 8 (1): e2531 DOI: 10.1038/cddis.2016.443
Image: Dr David Furness, Wellcome Images. Colour-enhanced image showing the stacked membrane discs of the Golgi complex (gold). A cluster of mitochondria (orange) are also present surrounded by cytoplasm.