New mechanisms for FUS induced neurodegenerative diseases are revealed.

On September 24th, the Proceedings of the National Academy of Sciences (PNAS) published an online study on fuS interacts with ATP synthase beta sub and mitochon unfoldingal bined response in and cellular and animal models, reporting on the interaction of RNA binding protein FUS with mitochondria at-based atmian at-to-beta sub-beta.
this study provides primary evidence for the RNA binding protein-targeted mitochondrial ATP synthase, and provides important research ideas for the future development of diagnostic tools and treatments for the treatment of neurodegenerative diseases associated with aging.
FUS (known as fused in sarcoma/translocated in liposarcoma, FUS/TLS) is a versatile DNA/RNA binding protein that is located primarily in the nucleus and can travel between the nucleus and the cytoplasm.
FUS proteins play an important role in RNA transcription, RNA splicing, and microRNA processing.
FUS protein disease is a group of fatal neurodegenerative diseases that affect a variety of neurons, including FUS-related prefrontal lobar degeneration/dementia and motor neuronal diseases such as amyotrophic lateral sclerosis, ALS-FUS.
more than 50 mutations have been found in FUS protein disease to affect the FUS gene, however, it is not clear how FUS protein causes the death of neuronal cells and the cellular and molecular mechanisms that cause neurodegenerative diseases.
the early work of Wu Wei's team successfully constructed a model of genetically modified fruit flies for FUS protein disease, which is a good simulation of the important pathological characteristics of FUS protein disease (Chen et al., 2011 Protein Cell).
subsequent study, using this genetically modified fruit fly model and combined with cell models and FTLD-FUS pathology samples, they found that FUS interacts with the mitochondrial molecular partner HSP60, which mediates to the mitochondrial body and causes mitochondrial damage, leading to the death of neuronal cells, suggesting that mitochondrial damage may become a new target for the treatment of FUS protein disease (Deng et al.2015 P.
In this study, researchers used an induced cell model of FUS protein disease to demonstrate that mitochondrial defects caused by FUS expression are early changes that occur before cell death.
in cell models and genetically modified fruit fly models, FUS enters the mitochondria and interacts with atP synthase beta subkey (ATP5B) in the mitochondria, disrupts the assembly of atP synthase complexes, inhibits the activity of mitochondrial ATP synthase, and activates mitochondrial defolding protein reaction (UPRmt).
at increased expression of ATP5B in cells and fruit flies expressing FUS, while reducing the expression of ATP5B or lowering the expression of the UPRmt gene can improve FUS-induced mitochondrial damage and neurodegenerative phenotypes.
FUS targeted mitochondrial ATP synthesis to activate UPRmt's findings, revealing a new mechanism for FUS induced neurodegenerative diseases, suggesting that mitochondrial damage may be a common mechanism for a variety of neurodegenerative diseases such as FTLD-FUS and ALS-FUS, and blocking mitochondrial damage may help treat these devastating diseases.
this work is mainly done by Wu Wei's research group, with Dr. Deng Jianwen and Doctoral Student Wang Peng as co-authors of the thesis, and Wu Wei and project researcher Zhu Wei as co-authors of the paper.
the research was funded by the National Natural Science Foundation of China and assisted by the Bioimaging Center of the Institute of Biophysics.
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