James B. Stewart
Max Planck Society
Publications 53
#1Roberta Filograna (KI: Karolinska Institutet)H-Index: 7
#2Camilla Koolmeister (KI: Karolinska Institutet)H-Index: 3
Last.Nils-Göran LarssonH-Index: 66
view all 11 authors...
Heteroplasmic mtDNA mutations typically act in a recessive way and cause mitochondrial disease only if present above a certain threshold level. We have experimentally investigated to what extent the absolute levels of wild-type (WT) mtDNA influence disease manifestations by manipulating TFAM levels in mice with a heteroplasmic mtDNA mutation in the tRNA Ala gene. Increase of total mtDNA levels ameliorated pathology in multiple tissues, although the levels of heteroplasmy remained the same. A red...
3 CitationsSource
#1Uwe Richter (UH: University of Helsinki)H-Index: 11
#2Kah Ying Ng (UH: University of Helsinki)H-Index: 1
Last.Brendan J. Battersby (UH: University of Helsinki)H-Index: 18
view all 18 authors...
Mitochondria have a compartmentalized gene expression system dedicated to the synthesis of membrane proteins essential for oxidative phosphorylation. Responsive quality control mechanisms are needed to ensure that aberrant protein synthesis does not disrupt mitochondrial function. Pathogenic mutations that impede the function of the mitochondrial matrix quality control protease complex composed of AFG3L2 and paraplegin cause a multifaceted clinical syndrome. At the cell and molecular level, defe...
4 CitationsSource
#1Sandra R. Bacman (UM: University of Miami)H-Index: 15
#2Johanna H.K. Kauppila (MPG: Max Planck Society)H-Index: 5
Last.Carlos T. Moraes (UM: University of Miami)H-Index: 68
view all 10 authors...
In the version of this article originally published, there was an error in Fig. 1a. The m.5024C>T mutation, shown as a green T, was displaced by one base. The error has been corrected in the print, HTML and PDF versions of this article.
#1Stanka Matic (MPG: Max Planck Society)H-Index: 5
#2Min Jiang (MPG: Max Planck Society)H-Index: 3
Last.Dusanka Milenkovic (MPG: Max Planck Society)H-Index: 25
view all 15 authors...
Replication of mammalian mitochondrial DNA (mtDNA) is an essential process that requires high fidelity and control at multiple levels to ensure proper mitochondrial function. Mutations in the mitochondrial genome maintenance exonuclease 1 (MGME1) gene were recently reported in mitochondrial disease patients. Here, to study disease pathophysiology, we generated Mgme1 knockout mice and report that homozygous knockouts develop depletion and multiple deletions of mtDNA. The mtDNA replication stallin...
11 CitationsSource
#1Sandra R. Bacman (UM: University of Miami)H-Index: 15
#2Johanna H.K. Kauppila (MPG: Max Planck Society)H-Index: 5
Last.Carlos T. Moraes (UM: University of Miami)H-Index: 68
view all 10 authors...
Mutations in the mitochondrial DNA (mtDNA) are responsible for several metabolic disorders, commonly involving muscle and the central nervous system1. Because of the critical role of mtDNA in oxidative phosphorylation, the majority of pathogenic mtDNA mutations are heteroplasmic, co-existing with wild-type molecules1. Using a mouse model with a heteroplasmic mtDNA mutation2, we tested whether mitochondrial-targeted TALENs (mitoTALENs)3,4 could reduce the mutant mtDNA load in muscle and heart. AA...
20 CitationsSource
#1Payam A. Gammage (MRC Mitochondrial Biology Unit)H-Index: 10
#2Carlo Viscomi (MRC Mitochondrial Biology Unit)H-Index: 23
Last.Michal Minczuk (MRC Mitochondrial Biology Unit)H-Index: 33
view all 16 authors...
Mutations of the mitochondrial genome (mtDNA) underlie a substantial portion of mitochondrial disease burden. These disorders are currently incurable and effectively untreatable, with heterogeneous penetrance, presentation and prognosis. To address the lack of effective treatment for these disorders, we exploited a recently developed mouse model that recapitulates common molecular features of heteroplasmic mtDNA disease in cardiac tissue: the m.5024C>T tRNAAla mouse. Through application of a pro...
23 CitationsSource
#1Sandra R. BacmanH-Index: 15
#2Claudia V. PereiraH-Index: 10
Last.Carlos T. MoraesH-Index: 68
view all 8 authors...
#1Johanna H.K. Kauppila (MPG: Max Planck Society)H-Index: 5
#2Nina A. Bonekamp (MPG: Max Planck Society)H-Index: 4
Last.Nils-Göran Larsson (KI: Karolinska Institutet)H-Index: 66
view all 8 authors...
9 CitationsSource
#1Marie-Lune Simard (MPG: Max Planck Society)H-Index: 5
#2Arnaud Mourier (University of Bordeaux)H-Index: 21
Last.James B. Stewart (MPG: Max Planck Society)H-Index: 25
view all 5 authors...
2 CitationsSource
#1Beverly J. McCann (University of Cambridge)H-Index: 2
#2Andy Cox (University of Cambridge)H-Index: 3
Last.Michal Minczuk (University of Cambridge)H-Index: 33
view all 6 authors...
Mitochondrial diseases often result from mutations in the mitochondrial genome (mtDNA). In most cases, mutant mtDNA coexists with wild-type mtDNA, resulting in heteroplasmy. One potential future approach to treat heteroplasmic mtDNA diseases is the specific elimination of pathogenic mtDNA mutations, lowering the level of mutant mtDNA below pathogenic thresholds. Mitochondrially targeted zinc-finger nucleases (mtZFNs) have been demonstrated to specifically target and introduce double-strand break...
2 CitationsSource