U.S. flag

An official website of the United States government

Dot gov

Official websites use .gov
A .gov website belongs to an official government organization in the United States.


Secure .gov websites use HTTPS
A lock ( ) or https:// means you’ve safely connected to the .gov website. Share sensitive information only on official, secure websites.


Main content area

Parkin expression reverses mitochondrial dysfunction in fused in sarcoma‐induced amyotrophic lateral sclerosis

S. J. Cha, H.‐J. Choi, H.‐J. Kim, E. J. Choi, K.‐H. Song, D. S. Im, K. Kim
Insect molecular biology 2020 v.29 no.1 pp. 56-65
DNA, Drosophila, RNA-binding proteins, adenosine triphosphate, amyotrophic lateral sclerosis, humans, imagos, larvae, mitochondria, muscle tissues, neuroprotective effect, neurotoxicity, pathogenesis, phenotype, protein content, protein synthesis, sarcoma
Fused in sarcoma (FUS) is a DNA/RNA‐binding protein associated with amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration. The exact molecular mechanisms by which FUS results in neurotoxicity have not yet been fully elucidated. Here, we found that parkin is a genetic suppressor of defective phenotypes induced by exogenous human wild type FUS in Drosophila. Although parkin overexpression did not modulate the FUS protein expression level, the locomotive defects in FUS‐expressing larvae and adult flies were rescued by parkin expression. We found that FUS expression in muscle tissues resulted in a reduction of the levels and assembly of mitochondrial complex I and III subunits, as well as decreased ATP. Remarkably, expression of parkin suppressed these mitochondrial dysfunctions. Our results indicate parkin as a neuroprotective regulator of FUS‐induced proteinopathy by recovering the protein levels of mitochondrial complexes I and III. Our findings on parkin‐mediated neuroprotection may expand our understanding of FUS‐induced ALS pathogenesis.