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Updated: Oct 13, 2025

Mitochondrial Respiration Quantification in Yeast Whole Cells
Published on: November 8, 2024
Mitochondrial respiration restricts Listeria monocytogenes infection by slowing down host cell receptor recycling
Anna Spier1, Michael G Connor2, Thomas Steiner3
1Evolutionary Biology of the Microbial Cell Unit, Institut Pasteur, Paris, France; Bacteria-Cell Interactions Unit, Institut Pasteur, Paris, France; Université de Paris, Paris, France; UMR2001, CNRS, Paris, France.
Abstract:
Mutations in mitochondrial genes impairing energy production cause mitochondrial diseases (MDs), 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 many pathogens. Here, we generate an epithelial cell model for one of the most common mitochondrial diseases, Leigh syndrome, by deleting surfeit locus protein 1 (SURF1), an assembly factor for respiratory chain complex IV. We use 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 the recycling of its host cell receptor c-Met, highlighting a previously undescribed role of mitochondrial respiration during infection.
Insights
Mitochondrial dysfunction increases susceptibility to bacterial infections like Listeria monocytogenes by affecting host cell entry. Enhancing mitochondrial energy metabolism can reduce infection rates, revealing a new role for mitochondria in immunity.
Area of Science:
- Cell Biology
- Infectious Diseases
- Mitochondrial Biology
Background:
- Mitochondrial diseases (MDs) impair energy production and are linked to increased bacterial infections.
- The role of mitochondrial dysfunction in host-pathogen interactions, particularly in epithelial cells, is poorly understood.
Purpose of the Study:
- To investigate the impact of mitochondrial respiration on bacterial infection in epithelial cells.
- To elucidate the mechanisms by which mitochondrial function influences pathogen entry and host defense.
Main Methods:
- Generated a Leigh syndrome epithelial cell model by deleting SURF1, a key factor in respiratory chain complex IV assembly.
- Modulated mitochondrial respiration rates using genetic and nutrient-based approaches.
- Assessed the entry efficiency of Listeria monocytogenes in relation to mitochondrial respiration levels.
Main Results:
- Impaired mitochondrial respiration significantly enhanced the entry of Listeria monocytogenes into epithelial cells.
- Increased mitochondrial energy metabolism reduced bacterial infection efficiency.
- Reduced endocytic recycling in cells with impaired mitochondrial respiration was observed, slowing the recycling of the c-Met receptor and dampening infection.
Conclusions:
- Mitochondrial respiration plays a critical role in regulating epithelial cell susceptibility to bacterial pathogens.
- Modulating mitochondrial function offers a potential strategy for controlling infections like Listeria monocytogenes.
- This study uncovers a novel mechanism involving mitochondrial respiration, endocytic recycling, and host-pathogen interactions.
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