Mitochondrial Respiration Restricts Listeria Monocytogenes Infection by Slowing Down Host Cell Receptor Recycling

Mutations in mitochondrial genes impairing energy production lead to mitochondrial diseases (MD) and clinical studies have shown that MD patients are prone to bacterial infections. However, the relationship between mitochondrial (dys)function and infection remains largely unexplored, especially in epithelial cells, the first barrier to pathogens. We generated an epithelial cell model for one of the most common MD, Leigh syndrome by deleting SURF1, an assembly factor for the respiratory chain complex IV. We employed this genetic model and a complementary, nutrient-based approach to modulate mitochondrial respiration rates and show that impaired mitochondrial respiration favors entry of the human pathogen Listeria monocytogenes, a well-established bacterial infection model. Reversely, enhanced mitochondrial energy metabolism decreases infection efficiency. We further demonstrate that endocytic recycling is reduced in mitochondrial respiration-dependent cells, dampening L. monocytogenes infection by slowing down recycling of its host cell receptor c-Met, highlighting a previously undescribed role of mitochondrial respiration during infection.