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Immunometabolic Circuits in Infection for Advancing Host Directed Therapies
Published on: September 13, 2024
Modulation of host mitochondrial dynamics during bacterial infection
Shaziya Khan1, Desh Raj1, Kritika Jaiswal2
1Pharmacology Division, CSIR-Central Drug Research Institute, Lucknow 226031, India; Academy of Scientific and Innovative Research (AcSIR), New Delhi 110001, India.
Abstract:
Mitochondria is a dynamic organelle of the cell that can regulate and maintain cellular ATP level, ROS production, calcium signaling and immune response. In order to retain their shape and distribution, mitochondria go through coordinated cycles of fission and fusion. Further, dysfunctional mitochondria are selectively eliminated from the cell via mitophagy to synchronize mitochondrial quality control and cellular homeostasis. In addition, mitochondria when in close proximity with the endoplasmic reticulum can alter the signaling pathways and some recent findings also reveal a direct correlation between the mitochondrial localization in the cell to the immune response elicited against the invading pathogen. These modulations in the mitochondrial network are collectively termed as 'mitochondrial dynamics'. Diverse bacteria, virus and parasitic pathogens upon infecting a cell can alter the host mitochondrial dynamics in favor of their multiplication and this in turn can be a major determinant of the disease outcome. Pharmacological perturbations in these pathways thus could lead to generation of additional therapeutic opportunities. This review will focus on the pathogenic modulation of the host mitochondrial dynamics, specifically during the bacterial infections and describes how dysregulated mitochondrial dynamics facilitates the pathogen's ability to establish efficient infection.
Insights
Pathogens disrupt cellular mitochondrial dynamics, impacting ATP levels and immune responses. Understanding these changes during bacterial infections offers new therapeutic avenues.
Area of Science:
- Cell Biology
- Immunology
- Microbiology
Background:
- Mitochondria are vital organelles regulating cellular energy, calcium, and immune signaling.
- Mitochondrial dynamics, involving fission, fusion, and mitophagy, maintain cellular homeostasis.
- Mitochondrial localization and dynamics are linked to immune responses against pathogens.
Purpose of the Study:
- To review how pathogens, particularly bacteria, manipulate host mitochondrial dynamics.
- To explore the role of altered mitochondrial dynamics in infection establishment and disease outcome.
- To highlight potential therapeutic strategies targeting mitochondrial dynamics.
Main Methods:
- Literature review focusing on bacterial pathogenesis and host cell responses.
- Analysis of studies investigating mitochondrial dynamics during infection.
- Synthesis of findings on the interplay between pathogens and mitochondrial networks.
Main Results:
- Pathogenic bacteria actively alter host mitochondrial dynamics to promote their survival and replication.
- Dysregulated mitochondrial dynamics can impair host immune defenses, facilitating infection.
- Mitochondrial dysfunction is a key factor in determining disease severity.
Conclusions:
- Targeting mitochondrial dynamics presents a promising therapeutic strategy against bacterial infections.
- Understanding pathogen-induced mitochondrial alterations is crucial for developing novel treatments.
- Mitochondrial dynamics play a critical role in host-pathogen interactions and disease progression.
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