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Andreazza 2019 Nat Commun
Additional label 2019-08  +
Coupling states OXPHOS  +
Has abstract Somatic mutations in the mitochondrial gen
Somatic mutations in the mitochondrial genome (mtDNA) have been linked to multiple disease conditions and to ageing itself. In ''Drosophila'', knock-in of a proofreading deficient mtDNA polymerase (POLG) generates high levels of somatic point mutations and also small indels, but surprisingly limited impact on organismal longevity or fitness. Here we describe a new mtDNA mutator model based on a mitochondrially-targeted cytidine deaminase, APOBEC1. ''mito''-APOBEC1 acts as a potent mutagen which exclusively induces C:G>T:A transitions with no indels or mtDNA depletion. In these flies, the presence of multiple non-synonymous substitutions, even at modest heteroplasmy, disrupts mitochondrial function and dramatically impacts organismal fitness. A detailed analysis of the mutation profile in the POLG and ''mito''-APOBEC1 models reveals that mutation type (quality) rather than quantity is a critical factor in impacting organismal fitness. The specificity for transition mutations and the severe phenotypes make ''mito''-APOBEC1 an excellent mtDNA mutator model for ageing research.
t mtDNA mutator model for ageing research.  +
Has editor [[Plangger M]]  +
Has info [https://www.ncbi.nlm.nih.gov/pubmed/31337756 PMID: 31337756 Open Access]  +
Has title Andreazza S, Samstag CL, Sanchez-Martinez
Andreazza S, Samstag CL, Sanchez-Martinez A, Fernandez-Vizarra E, Gomez-Duran A, Lee JJ, Tufi R, Hipp MJ, Schmidt EK, Nicholls TJ, Gammage PA, Chinnery PF, Minczuk M, Pallanck LJ, Kennedy SR, Whitworth AJ (2019) Mitochondrially-targeted APOBEC1 is a potent mtDNA mutator affecting mitochondrial function and organismal fitness in Drosophila. Nat Commun 10:3280.
fitness in Drosophila. Nat Commun 10:3280.  +
Instrument and method Oxygraph-2k  +
Mammal and model Drosophila  +
MiP area Respiration  + , mtDNA;mt-genetics  + , Genetic knockout;overexpression  +
Pathways N  + , S  +
Preparation Homogenate  +
Was published in journal Nat Commun +
Was published in year 2019  +
Was written by Andreazza S + , Samstag CL + , Sanchez-Martinez A + , Fernandez-Vizarra E + , Gomez-Duran A + , Lee JJ + , Tufi R + , Hipp MJ + , Schmidt EK + , Nicholls TJ + , Gammage PA + , Chinnery PF + , Minczuk M + , Pallanck LJ + , Kennedy SR + , Whitworth AJ +
Categories Publications
Modification date
"Modification date" is a predefined property that corresponds to the date of the last modification of a subject and is provided by Semantic MediaWiki.
08:40:07, 9 August 2019  +
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