The body’s ability to adapt to changing conditions and shifting physiologic demands is essential to its survival. To ensure cellular performance and the health of the entire organism, each cell must be able to dispose of damaged or unnecessary proteins.
Now, a study from the Blavatnik Institute at Harvard Medical School (HMS) shows that intense exercise, fasting, and an array of hormones can activate cells’ built-in protein-disposal systems and enhance their ability to purge defective, toxic, or unneeded proteins.
The findings, published Feb. 19 in PNAS, reveal a previously unknown mechanism that is triggered by fluctuations in hormone levels, which signal changes in physiologic conditions.
“Our findings show that the body has a built-in mechanism for cranking up the molecular machinery responsible for waste-protein removal that is so critical for the cells’ ability to adapt to new conditions,” said Alfred Goldberg, senior author on the study and professor of cell biology at the Blavatnik Institute.
Cellular housecleaning in disease and health
Malfunctions in the cells’ protein-disposal machinery can lead to the accumulation of misfolded proteins, which clog up the cell, interfere with its functions, and, over time, precipitate the development of diseases, including neurodegenerative conditions such as amyotrophic lateral sclerosis and Alzheimer’s.
The best-studied biochemical system used by cells to remove junk proteins is the ubiquitin-proteasome pathway. It involves tagging defective or unneeded proteins with ubiquitin molecules — a process known as the “kiss of death” — marking them for destruction by the cell’s protein-disposal unit, known as 26S proteasome.
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