Yardeni 2023 MiP2023

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MiPschool 2023

Yardeni 2023 MiP2023

Yardeni Tal
The host immune system and the gut microbiota are regulated by the mitochondrial DNA.

Link: MiP2023 Obergurgl AT

Yardeni Tal (2023)

Event: MiP2023 Obergurgl AT

Authors: Yardeni Tal

Both mitochondrial DNA (mtDNA) lineages and the gut microbiota have been correlated with altered risk for a variety of human diseases including obesity. However, the mechanisms by which mtDNA variation and the gut microbiota modulate disease risk remains unknown. Our hypothesis is that both the gut microbiota and the immune system are modulated by the mitochondrial genome, in part through mitochondrial reactive oxygen species (mtROS) production, forming a critical link between the gut microbiota and disease initiation and progression. Our studies showed significant differences in gut microbiota in our conplastic mice which differ in their mtDNA lineages. Further, the transfer of the gut microbiota from a host of one mitochondrial genotype to a host of different mitochondrial genotypes shifted the gut microbiota composition toward that of the recipient animal. Moreover, we showed that host mtROS levels modulated the composition of the gut microbiota.
Those conplastic mice also exhibit markedly different capacities to sustain melanoma tumor growth. Relative to control mtDNA (mtDNAB6) mice, the mice harboring NZB mtDNAs (mtDNANZB) have strong anti-tumor immune response while those with129 mtDNA (mtDNA129) are the opposite. Reduction of mtROS by expression of mitochondrial catalase (mtCAT)Tg only in the hematopoietic cells changed the gut microbiota and obviated the anti-tumor effects on the mtDNANZB and mtDNAB6 mice. These observations suggest that disease severity (melanoma), and gut microbiota are regulated by the mtDNA's regulation of mtROS production in host immune cells, pointing to new potential pathways for understanding diseases etiology.

β€’ O2k-Network Lab: IL Ramat Gan Yardeni T


Event: Oral 

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