Analyzing the suppression of respiratory defects in the yeast model of human mitochondrial tRNA diseases

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• 作者：Arianna Montanari ; You Fang Zhou ; Mario Fazzi D'Orsi ; Monique Bolotin-Fukuhara ; Laura Frontali ; Silvia Francisci
• 关键词：mt ; mitochondrial ; bp ; base-pair ; MELAS ; mitochondrial encephalomyophathy ; lactic acidosis ; and stroke-like episodes ; aa ; amino acid(s) ; aa-RS ; aminoacyl-tRNA synthetase ; rho+ ; mt DNA wild-type ; rho ; mt DNA absent ; NAM2 ; gene coding for the yeast mitochon
• 刊名：Gene
• 出版年：2013
• 出版时间：15 September, 2013
• 年：2013
• 卷：527
• 期：1
• 页码：1-9
• 全文大小：747 K

文摘

The respiratory defects associated with mutations in human mitochondrial tRNA genes can be mimicked in yeast, which is the only organism easily amenable to mitochondrial transformation. This approach has shown that overexpression of several nuclear genes coding for factors involved in mitochondrial protein synthesis can alleviate the respiratory defects both in yeast and in human cells.

The present paper analyzes in detail the effects of overexpressed yeast and human mitochondrial translation elongation factors EF-Tu. We studied the suppressing activity versus the function in mt translation of mutated versions of this factor and we obtained indications on the mechanism of suppression.

Moreover from a more extended search for suppressor genes we isolated factors which might be active in mitochondrial biogenesis. Results indicate that the multiplicity of mitochondrial factors as well as their high variability of expression levels can account for the variable severity of mitochondrial diseases and might suggest possible therapeutic approaches.