Projects per year
Abstract
Mitochondria are organelles of all nucleated cells, and variations in mtDNA sequence affect a wide spectrum of human diseases. However, animal models for mtDNA-associated diseases are rare, making it challenging to explore mechanisms underlying the contribution of mitochondria. Here, we identify a polymorphism in the mitochondrial genome, G-to-T at position 7778, which results in an aspartic acid-to-tyrosine (D-Y) substitution in the fifth amino acid of the highly conserved N-terminus of ATP synthase 8 (ATP8). Using a series of conplastic strains we show that this polymorphism increases susceptibility to multiple autoimmune diseases, including collagen-induced arthritis, autoimmune diabetes, nephritis and autoimmune pancreatitis. In addition, it impairs reproductive performance in females, but only in the MRL/MpJ strain. We also demonstrate that the mtAtp8 polymorphism alters mitochondrial performance, increasing H2O2 production and affecting mitochondrial structure. Functional analysis reveals that the polymorphism increase the CD4 T cell adaptive potential to an oxidative phosphorylation impaired condition. Our findings provide direct experimental evidence for the role of mitochondria in autoimmunity and reproduction.
Original language | English |
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Journal | Human Molecular Genetics |
Volume | 18 |
Issue number | 24 |
Pages (from-to) | 4689-4698 |
Number of pages | 10 |
ISSN | 0964-6906 |
DOIs | |
Publication status | Published - 26.11.2009 |
Research Areas and Centers
- Academic Focus: Center for Infection and Inflammation Research (ZIEL)
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Dive into the research topics of 'The mtDNA nt7778 G/T polymorphism affects autoimmune diseases and reproductive performance in the mouse'. Together they form a unique fingerprint.Projects
- 1 Finished
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The role of Toll like receptor 4 in the pathogenesis of collagen-induced arthritis
Ibrahim, S. & Pierer, M.
01.01.05 → 31.12.09
Project: DFG Projects › DFG Individual Projects