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Roles of microglial mitophagy in neurological disorders
Yang Liu1,2, Miao Wang1,2, Xiao-Ou Hou1,2
1Department of Neurology and Clinical Research Center of Neurological Disease, The Second Affiliated Hospital of Soochow University, Suzhou, China.
Abstract:
Microglia are the resident innate immune cells in the central nervous system (CNS) that serve as the first line innate immunity in response to pathogen invasion, ischemia and other pathological stimuli. Once activated, they rapidly release a variety of inflammatory cytokines and phagocytose pathogens or cell debris (termed neuroinflammation), which is beneficial for maintaining brain homeostasis if appropriately activated. However, excessive or uncontrolled neuroinflammation may damage neurons and exacerbate the pathologies in neurological disorders. Microglia are highly dynamic cells, dependent on energy supply from mitochondria. Moreover, dysfunctional mitochondria can serve as a signaling platform to facilitate innate immune responses in microglia. Mitophagy is a means of clearing damaged or redundant mitochondria, playing a critical role in the quality control of mitochondrial homeostasis and turnover. Mounting evidence has shown that mitophagy not only limits the inflammatory response in microglia but also affects their phagocytosis, whereas mitochondria dysfunction and mitophagy defects are associated with aging and neurological disorders. Therefore, targeting microglial mitophagy is a promising therapeutic strategy for neurological disorders. This article reviews and highlights the role and regulation of mitophagy in microglia in neurological conditions, and the research progress in manipulating microglial mitophagy and future directions in this field are also discussed.
Insights
Microglia, the brain's immune cells, rely on mitophagy to clear damaged mitochondria. Enhancing mitophagy in microglia offers a promising therapeutic strategy for neurological disorders.
Area of Science:
- Neuroscience
- Immunology
- Cell Biology
Background:
- Microglia are central nervous system immune cells crucial for brain homeostasis.
- Dysfunctional mitochondria and impaired mitophagy contribute to neuroinflammation and neurological disorders.
- Mitophagy, the selective removal of damaged mitochondria, is vital for microglial function and energy regulation.
Purpose of the Study:
- To review the role and regulation of mitophagy in microglia within the context of neurological conditions.
- To highlight current research on manipulating microglial mitophagy for therapeutic benefit.
- To discuss future directions in targeting microglial mitophagy.
Main Methods:
- Literature review of studies on microglia, mitochondria, mitophagy, and neurological disorders.
- Analysis of the regulatory mechanisms of mitophagy in microglia.
- Synthesis of research progress in therapeutic interventions targeting microglial mitophagy.
Main Results:
- Mitophagy is essential for maintaining microglial homeostasis, regulating inflammatory responses, and supporting phagocytosis.
- Defects in mitophagy are linked to aging and the exacerbation of neurological pathologies.
- Targeting microglial mitophagy presents a promising therapeutic avenue for various neurological conditions.
Conclusions:
- Microglial mitophagy plays a critical role in neuroinflammation and neurological disease pathogenesis.
- Modulating mitophagy in microglia holds significant therapeutic potential for treating neurological disorders.
- Further research into the precise mechanisms and therapeutic applications of microglial mitophagy is warranted.
