Mitochondrial fission mediates an evolutionarily conserved antibacterial defense response

Area of Science:

• Cell Biology
• Immunology
• Microbiology

Background:

• Animals utilize diverse immune mechanisms to combat infections.
• Mitochondria play crucial roles in cellular processes, including immunity.

Purpose of the Study:

• To investigate the role of mitochondrial fission in host defense against bacterial pathogens.
• To elucidate the molecular pathways linking mitochondrial fission to antibacterial responses.

Main Methods:

• Macrophages and *Caenorhabditis elegans* were challenged with *Escherichia coli*.
• Mitochondrial fission, mitochondrial unfolded protein response (UPR^mt), and lipid droplet production were analyzed.
• The effect of inhibiting histone deacetylase 6 (HDAC6) on host defense was assessed.

Main Results:

• *Escherichia coli* infection induced mitochondrial fission, promoting bacterial clearance.
• Mitochondrial fission triggered UPR^mt and lipid droplet production, which cross-regulated each other.
• The pathogen *Salmonella enterica* suppressed mitochondrial fission, but inhibition of HDAC6 restored fission, lipid droplet production, and bacterial clearance.

Conclusions:

• Mitochondrial fission is an evolutionarily conserved host defense mechanism against bacterial infections.
• This pathway involves UPR^mt and lipid droplet induction, suggesting a coordinated immune response.
• Targeting mitochondrial fission presents a potential strategy for developing new anti-infective therapies.