Sci Adv: The "three brothers" of Parkinson's disease, cancer, and type 2 diabetes are originally in the same line

When the cell is under pressure, a chemical alarm will sound, which initiates a series of activities to protect the core part of the cell.

Salk researchers found a direct connection between the main sensors of cellular stress and Parkin itself.

Science Advances

Parkin's job is to remove mitochondria that have been damaged by cellular stress so that new mitochondria can take their place.

Shaw's laboratory is known for its work in the areas of metabolism and cancer, and it has spent years studying in depth how cells regulate the cell's more general cell cleaning and recycling process, namely autophagy.

The AMPK enzyme controls autophagy by activating an enzyme called ULK1, which is highly sensitive to a variety of cellular stresses including mitochondrial damage.

In order to confirm the correctness of the research results, the research team used mass spectrometry to accurately reveal the position where ULK1 attaches the phosphate group to Parkin.

Push Push measure which might be "warning" signal is sent to Parkin by AMPK ULK1, let Parkin after the first wave of strikes to check the damage mitochondria and triggers the destruction of those severely impaired mitochondrial function and can not be restored if necessary.

Mutations in the phosphorylation site of ULK1 in arkin, inherited AMPK or ULK1 depletion, or drug-induced ULK1 inhibition, will cause the delay of Parkin activation, as well as defects in the detection of Parkin function and downstream mitotic events.

At time 0, Parkin protein (green signal) and mitochondria (red signal) are located in different parts of the cell (left image), but co-localize with mitochondria after 60 minutes (right image)

Maximum Parkin activity depends on the Parkin phosphorylation of ULK1

Maximum Parkin activity depends on the Parkin phosphorylation of ULK1

These findings have broad implications.

AMPK is the core sensor of cell metabolism.

Changes in metabolism and mitochondrial health are critical in cancer, diabetes, and neurodegenerative diseases.

sciencemag.

sciencemag.
org/content/7/15/eabg4544" target="_blank" rel="noopener">AMPK / ULK1-mediated phosphorylation of Parkin ACT domain mediates an early step in mitophagy

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