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.

Cell Reports
|November 10, 2021
PubMed

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.

Related Concept Videos

The Electron Transport Chain01:30

The Electron Transport Chain

The electron transport chain or oxidative phosphorylation is an exothermic process in which free energy released during electron transfer reactions is coupled to ATP synthesis. This process is a significant source of energy in aerobic cells, and therefore inhibitors of the electron transport chain can be detrimental to the cell's metabolic processes.
Inhibitors of the electron transport chain
Rotenone, a widely used pesticide, prevents electron transfer from Fe-S cluster to ubiquinone or Q...
18.1K
Electron Transport Chain: Complex I and II01:46

Electron Transport Chain: Complex I and II

The mitochondrial electron transport chain (ETC) is the main energy generation system in the eukaryotic cells. However, mitochondria also produce cytotoxic reactive oxygen species (ROS) due to the large electron flow during oxidative phosphorylation. While Complex I is one of the primary sources of superoxide radicals, ROS production by Complex II is uncommon and may only be observed in cancer cells with mutated complexes.
ROS generation is regulated and maintained at moderate levels necessary...
15.3K
Recycling Endosomes and Transcytosis00:58

Recycling Endosomes and Transcytosis

The recycling endosome, also known as the endosomal recycling compartment (ERC), is a part of the slow-recycling process of the endocytic pathway. Molecules internalized through receptor-mediated endocytosis are either degraded in the lysosomes or are recycled to the plasma membrane through the fast- or slow-recycling route.
The recycling endosome is not a single organelle but an extensively tubulated network of recycling pathways. It functions in storing molecules or transporting them across...
2.9K
Mitochondrial Membranes01:45

Mitochondrial Membranes

A single mitochondrion is a bean-shaped organelle enclosed by a double-membrane system. The outer membrane of mitochondria is smooth and contains many porins - the integral membrane transporters. Porins enable free diffusion of ions and small uncharged molecules through the outer mitochondrial membrane but limit the transport of molecules larger than 5000 Daltons. Further, the outer mitochondrial membrane forms a unique structure called membrane contact sites with other subcellular organelles,...
12.9K