Mysterious microproteins have major implications for human disease.
Salk Institute.
phys.org/news/2019-10-myste...
"PIGBOS is like a connection to link mitochondria and ER together," says Chu. "We hadn't seen that before in microproteins—and it's rare in just normal proteins."
The researchers found that PIGBOS actually communicates with CLCC1 to regulate stress in the ER. Without PIGBOS, the ER is more likely to experience stress, which leads to a chain of events where the cell tries to clear out harmful misshapen proteins (called the unfolded protein response). If the cell fails to dispose of these proteins, it will initiate a self-destruct sequence and die.
The scientists were not expecting to see a role for a mitochondrial protein in the unfolded protein response. This new understanding of PIGBOS opens the door to future therapies that can target cell stress.
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Regulation of the ER stress response by a mitochondrial microprotein.
Qian Chu, Thomas F. Martinez, […]Alan Saghatelian.
Nature Communications volume 10, Article number: 4883 (2019).
nature.com/articles/s41467-...
Discussion
Understanding how cells respond to stress is of importance. These pathways are required for maintaining homeostasis and cell health, and their dysregulation can lead to disease. For example, UPR dysfunction contributes to accumulation of key disease-related proteins, and thus plays an essential role in the pathogenesis of many neurodegenerative disorders, including Alzheimer’s disease, Parkinson’s disease, and Huntington’s disease14,15. Cells with an insufficient capacity to handle protein production begin to accumulate unfolded or misfolded proteins, which causes ER stress and triggers UPR.
Mitochondria?
Parkinson's disease is an autoimmune disease: An emerging viewpoint
L-Serine prevents protein from misfolding.
