Abstract
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 enhances host ATP production by boosting the oxidative phosphorylation metabolic pathway. Furthermore, Rv1813c appears to differentially modulate the host cell response to oxidative stress. Expression of Rv1813 in host cells inhibits the release of cytochrome c from mitochondria, an early apoptotic event, in response to short-term oxidative stress. However, Rv1813c expressing cells showed increased sensitivity to prolonged stress. This study reveals a novel class of mitochondria targeting effectors from Mtb and opens new research directions on host metabolic reprogramming and apoptosis control.