Amazing stuff! Cancer is history! Fountain of youth! Parkinson's disease and diabetes!
"... “Our findings represent the earliest step in Parkin’s alarm response that anyone’s ever found by a long shot. All the other known biochemical events happen at one hour; we’ve now found something that happens within five minutes,” ...
Parkin’s job is to clear away mitochondria that have been damaged by cellular stress so that new ones can take their place, a process called mitophagy. However, Parkin is mutated in familial Parkinson’s disease, making the protein unable to clear away damaged mitochondria. ...
[researchers] began searching for autophagy-related proteins directly activated by ULK1. They screened about 50 different proteins, expecting about 10 percent to fit. They were shocked when Parkin topped the list. Biochemical pathways are usually very convoluted, involving up to 50 participants, each activating the next. Finding that a process as important as mitophagy is initiated by only three participants—first AMPK, then ULK1, then Parkin—was so surprising that [researchers] could scarcely believe it. ...
The findings have wide-ranging implications. AMPK, the central sensor of the cell’s metabolism, is itself activated by a tumor suppressor protein called LKB1 that is involved in a number of cancers, ... and it is activated by a type 2 diabetes drug called metformin. Meanwhile, numerous studies show that diabetes patients taking metformin exhibit lower risks of both cancer and aging comorbidities. Indeed, metformin is currently being pursued as one of the first ever “anti-aging” therapeutics in clinical trials. ..."
Parkin’s job is to clear away mitochondria that have been damaged by cellular stress so that new ones can take their place, a process called mitophagy. However, Parkin is mutated in familial Parkinson’s disease, making the protein unable to clear away damaged mitochondria. ...
[researchers] began searching for autophagy-related proteins directly activated by ULK1. They screened about 50 different proteins, expecting about 10 percent to fit. They were shocked when Parkin topped the list. Biochemical pathways are usually very convoluted, involving up to 50 participants, each activating the next. Finding that a process as important as mitophagy is initiated by only three participants—first AMPK, then ULK1, then Parkin—was so surprising that [researchers] could scarcely believe it. ...
The findings have wide-ranging implications. AMPK, the central sensor of the cell’s metabolism, is itself activated by a tumor suppressor protein called LKB1 that is involved in a number of cancers, ... and it is activated by a type 2 diabetes drug called metformin. Meanwhile, numerous studies show that diabetes patients taking metformin exhibit lower risks of both cancer and aging comorbidities. Indeed, metformin is currently being pursued as one of the first ever “anti-aging” therapeutics in clinical trials. ..."
"... Phosphorylation of Parkin Ser108 occurs maximally within five minutes of mitochondrial damage, unlike activation of PINK1 and TBK1, which is observed thirty to sixty minutes later. Mutation of the ULK1 phosphorylation sites in Parkin, genetic AMPK or ULK1 depletion, or pharmacologic ULK1 inhibition, all lead to delays in Parkin activation and defects in assays of Parkin function and downstream mitophagy events. These findings reveal an unexpected first step in the mitophagy cascade."
Here is the underlying research article:
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