|Title||Knockdown of APOPT1/COA8 Causes Cytochrome Oxidase Deficiency, Neuromuscular Impairment, and Reduced Resistance to Oxidative Stress in Drosophila melanogaster.|
|Publication Type||Journal Article|
|Year of Publication||2019|
|Authors||Brischigliaro, M, Corrà, S, Tregnago, C, Fernandez-Vizarra, E, Zeviani, M, Costa, R, De Pittà, C|
Cytochrome oxidase (COX) deficiency is the biochemical hallmark of several mitochondrial disorders, including subjects affected by mutations in (), recently renamed as (HGNC:20492). Loss-of-function mutations are responsible for a specific infantile or childhood-onset mitochondrial leukoencephalopathy with a chronic clinical course. Patients deficient in COA8 show specific COX deficiency with distinctive neuroimaging features, i.e., cavitating leukodystrophy. In human cells, COA8 is rapidly degraded by the ubiquitin-proteasome system, but oxidative stress stabilizes the protein, which is then involved in COX assembly, possibly by protecting the complex from oxidative damage. However, its precise function remains unknown. The gene () is the ortholog of human encoding a highly conserved COA8 protein. We report that knockdown (KD) flies show locomotor defects, and other signs of neurological impairment, reduced COX enzymatic activity, and reduced lifespan under oxidative stress conditions. Our data indicate that KD of in phenocopies several features of the human disease, thus being a suitable model to characterize the molecular function/s of this protein and the pathogenic mechanisms associated with its defects.
|Alternate Journal||Front Physiol|
|PubMed Central ID||PMC6742693|