A Mycobacterium tuberculosis effector targets mitochondrion, controls energy metabolism and limits cytochrome c exit.

Martin, M.; deVisch, A.; Barthe, P.; Turapov, O.; Aydogan, T.; Heriaud, L.; Gracy, J.; Mukamolova, G.; Letourneur, F.; Cohen-Gonsaud, M.

doi:10.1101/2021.01.31.428746

bioRxiv · 10.1101/2021.01.31.428746

A Mycobacterium tuberculosis effector targets mitochondrion, controls energy metabolism and limits cytochrome c exit.

Martin, M.·deVisch, A.·Barthe, P.·Turapov, O.·Aydogan, T.·Heriaud, L.·Gracy, J.·Mukamolova, G.·Letourneur, F.·Cohen-Gonsaud, M.

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Abstract

Host metabolism reprogramming is a key feature of Mycobacterium tuberculosis (Mtb) infection that enables the survival of this pathogen within phagocytic cells and modulates the immune response facilitating the spread of the tuberculosis disease. Here, we demonstrate that a previously uncharacterized secreted protein from Mtb, Rv1813c manipulates the host metabolism by targeting mitochondria. When expressed in eukaryotic cells, the protein is delivered to the mitochondrial intermembrane space and promotes the enhancement of host ATP production by boosting the oxidative phosphorylation metabolic pathway. Furthermore, the release of cytochrome c from mitochondria, an early apoptotic event in response to short-term oxidative stress, is delayed in Rv1813c expressing cells. This study reveals a novel class of mitochondria targeting effectors from Mtb which might participate in host cells metabolic reprogramming and apoptosis control during Mtb infections.

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Martin, M., deVisch, A., Barthe, P., Turapov, O., Aydogan, T., Heriaud, L., Gracy, J., Mukamolova, G., Letourneur, F., Cohen-Gonsaud, M.. 2021-01-31. A Mycobacterium tuberculosis effector targets mitochondrion, controls energy metabolism and limits cytochrome c exit.. https://doi.org/10.1101/2021.01.31.428746

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