Reduced Energy Production In Brain Cells Is Linked To Cognitive Decline

Protein clumping is a hallmark of diabetes and many neurodegenerative diseases including Alzheimer’s, Parkinson’s and Huntington’s disease. If our cells cannot remove these protein clumps, the cells’ ability to generate energy is reduced. A new study has shed light on the internal quality control system that may be responsible for the removal of protein clumps. This study made global medical and scientific headlines in October 2017.


  • An in vitro study


  • The findings need to be verified in a study using human tissue biopsy samples


  • Healthy cells produce dysfunctional clumping proteins with tails (CAT-tailed proteins) when there is an occasional decrease in cellular energy
  • CAT-tailed proteins clump and accumulate in the mitochondria, preventing mitochondria from producing energy
  • When too many brain cells have been affected, irreversible damage occurs


  • This study identified a new quality control pathway in the brain cells
  • The quality control pathway protects the mitochondria from the toxic effects of CAT-tail proteins by preventing the addition of the CAT-tail to dysfunctional proteins. This allows the cell’s quality control system to remove dysfunctional proteins from the cell
  • If cells lack energy, these CAT-tailed proteins cannot be removed by the quality control pathway. They accumulate in the brain cells and gradually strangulate the cell and prevent the mitochondria from making sufficient energy to support the functions of the brain cell. Eventually, the changes become irreversible and the affected brain cell is permanently damaged
  • Defects in the quality control pathway or its age-dependent decline may be the cause of human diseases associated with mitochondrial dysfunction and neurodegeneration

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Izawa,T., Park, S-H., Zhao, L., Hartl, F.U., and Neupert, W. (2017) Cytosolic protein Vms1 links ribosome quality control to mitochondrial and cellular homeostasis. Cell DOI: 10.1016/j.cell.2017.10.002