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High-throughput Quantitative Real-time RT-PCR Assay for Determining Expression Profiles of Types I and III Interferon Subtypes
Published on: March 24, 2015
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Nuclear response to divergent mitochondrial DNA genotypes modulates the interferon immune response
M Isabel G Lopez Sanchez1,2, Mark Ziemann3,4, Annabell Bachem5
1Centre for Eye Research Australia, Royal Victorian Eye and Ear Hospital, Melbourne, Victoria, Australia.
Plos One
|October 8, 2020
Summary
Mitochondrial genetic differences can alter immune responses, even without affecting energy production. This study shows how introducing foreign mitochondrial DNA impacts interferon signaling and viral defense in mice.
Area of Science:
- Cellular Biology
- Immunology
- Genetics
Background:
- Mitochondrial oxidative phosphorylation (OXPHOS) is crucial for cellular energy. Its biogenesis requires coordination between nuclear and mitochondrial genomes, highlighting nuclear-mitochondrial genetic communication.
- Nuclear-mitochondrial genetic divergence presents unique challenges to cellular function and immune response.
Purpose of the Study:
- To investigate the transcriptomic and functional consequences of nuclear-mitochondrial genetic divergence.
- To model varying degrees of genetic divergence using xenomitochondrial cybrid cell lines and a xenomitochondrial mouse model.
Main Methods:
- Created xenomitochondrial cybrid cell lines with mouse nuclear DNA and divergent mouse mitochondrial DNA (mtDNA).
- Developed a xenomitochondrial mouse model with specific nuclear and mtDNA origins.
- Performed RNA sequencing on cybrids and analyzed immune responses in mice.
Main Results:
- Xenomitochondrial cybrids showed activated interferon signaling pathways, independent of OXPHOS dysfunction.
- Xenomitochondrial mice exhibited reduced baseline interferon expression and impaired innate immune response to herpes simplex virus.
- Viral control was decreased in xenomitochondrial mice upon immune challenge.
Conclusions:
- Nuclear-mitochondrial genetic divergence, through exogenous mtDNA, modulates interferon immune responses in vitro and in vivo, even without compromising OXPHOS.
- Findings suggest a role for mitochondrial genetic variation in immune function, potentially relevant to mitochondrial disease patients' susceptibility to infections.
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