Biochimica et biophysica acta
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Biochim. Biophys. Acta · Sep 2016
Delineating the relationship between amyotrophic lateral sclerosis and frontotemporal dementia: Sequence and structure-based predictions.
Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are related neurodegenerative disorders which are characterized by a rapid decline in cognitive and motor functions, and short survival. Both syndromes may be present within the same family or even in the same person. The genetic findings for both diseases also support the existence of a continuum, with mutations in the same genes being found in patients with ALS, FTD or FTD/ALS. ⋯ We found a trend that energy changes are higher for ALS compared to FTD mutations. The stability of the ALS mutants correlated well with the duration of disease progression as compared to FTD-ALS mutants. This study provides a comprehensive understanding of the mechanism of ALS and illustrates the significance of structure-energy based studies in differentiating ALS and FTD mutations.
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Biochim. Biophys. Acta · Sep 2016
Disruption of the human COQ5-containing protein complex is associated with diminished coenzyme Q10 levels under two different conditions of mitochondrial energy deficiency.
The Coq protein complex assembled from several Coq proteins is critical for coenzyme Q6 (CoQ6) biosynthesis in yeast. Secondary CoQ10 deficiency is associated with mitochondrial DNA (mtDNA) mutations in patients. We previously demonstrated that carbonyl cyanide-p-trifluoromethoxyphenylhydrazone (FCCP) suppressed CoQ10 levels and COQ5 protein maturation in human 143B cells. ⋯ The findings elucidate a possible mechanism for mitochondrial dysfunction-induced CoQ10 deficiency in human cells.