Good news! Already patented!
"... In experiments with human kidney cells, the research team reported, adding a small molecule called SP11 to the fragmented mitochondria made them hale and whole again.
The team described their work in a May 6 report in Nature Communications, and Stanford has patented SP11 as a potential candidate for drug development. ..."
From the abstract:
"Fis1-mediated mitochondrial localization of Drp1 and excessive mitochondrial fission occur in human pathologies associated with oxidative stress. However, it is not known how Fis1 detects oxidative stress and what structural changes in Fis1 enable mitochondrial recruitment of Drp1.
We find that conformational change involving α1 helix in Fis1 exposes its only cysteine, Cys41. In the presence of oxidative stress, the exposed Cys41 in activated Fis1 forms a disulfide bridge and the Fis1 covalent homodimers cause increased mitochondrial fission through increased Drp1 recruitment to mitochondria.
Our discovery of a small molecule, SP11, that binds only to activated Fis1 by engaging Cys41, and data from genetically engineered cell lines lacking Cys41 strongly suggest a role of Fis1 homodimerization in Drp1 recruitment to mitochondria and excessive mitochondrial fission.
The structure of activated Fis1-SP11 complex further confirms these insights related to Cys41 being the sensor for oxidative stress.
Importantly, SP11 preserves mitochondrial integrity and function in cells during oxidative stress and thus may serve as a candidate molecule for the development of treatment for diseases with underlying Fis1-mediated mitochondrial fragmentation and dysfunction."
A hidden cysteine in Fis1 targeted to prevent excessive mitochondrial fission and dysfunction under oxidative stress (open access)
... researchers found a small molecule called SP11 that prevents damage to mitochondria (purple) ... caused by exposure to oxidating chemicals. It has potential for treating mitochondria-associated ailments like ALS, heart disease and diabetes, in which oxidating chemicals are formed in the body. Healthy mitochondria (left) split and unite all the time as a way to exchange components that are required to maintain their quality. Adding an oxidizing agent like hydrogen peroxide (center) kept mitochondria from dividing into equal halves and snipped them into useless fragments instead. The addition of SP11 (right) made the mitochondria healthy and whole again.
Top: A protein called Drp1 (blue) prompts the cell’s power plants, mitochondria (tan), to divide. Drp1 normally acts through a go-between protein called Mff (green).
Bottom: But when exposure to oxidizing chemicals stresses mitochondria, another go-between protein, Fis1 (pink) hijacks the division process, squeezing mitochondria into unequal parts. Those parts fracture into smaller and smaller fragments until they can’t produce enough energy to keep the cell healthy. The damage spreads from cell to cell and causes a variety of human ailments, including Parkinson’s and heart disease.
Fig. 7: SP11 reduces H2O2-induced mitochondrial ROS production and fragmentation and increased Drp1 translocation to the mitochondria.
No comments:
Post a Comment