Andreazza 2019 Nat Commun
|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. https://doi.org/10.1038/s41467-019-10857-y|
» Nat Commun 10:3280. PMID: 31337756 Open Access
Andreazza Simonetta, Samstag Colby L, Sanchez-Martinez Alvaro, Fernandez-Vizarra Erika, Gomez-Duran Aurora, Lee Juliette J, Tufi Roberta, Hipp Michael J, Schmidt Elizabeth K, Nicholls Thomas J, Gammage Payam A, Chinnery Patrick F, Minczuk Michal, Pallanck Leo J, Kennedy Scott R, Whitworth Alexander J (2019) Nat Commun
Abstract: 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.
• Bioblast editor: Plangger M • O2k-Network Lab: UK Cambridge Whitworth A
Labels: MiParea: Respiration, mtDNA;mt-genetics, Genetic knockout;overexpression
Coupling state: OXPHOS Pathway: N, S HRR: Oxygraph-2k