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Updated: Jun 9, 2025
Two-photon Imaging of Microglial Processes' Attraction Toward ATP or Serotonin in Acute Brain Slices
Published on: January 31, 2019
Mitochondria are absent from microglial processes performing surveillance, chemotaxis, and phagocytic engulfment
Alicia N Pietramale1, Xhoela Bame1, Megan E Doty1
1Department of Biological Sciences, Dartmouth College, Hanover NH, USA.
Abstract:
Microglia continually surveil the brain allowing for rapid detection of tissue damage or infection. Microglial metabolism is linked to tissue homeostasis, yet how mitochondria are subcellularly partitioned in microglia and dynamically reorganize during surveillance, injury responses, and phagocytic engulfment in the intact brain are not known. Here, we performed intravital imaging of microglia mitochondria, revealing that microglial processes diverge, with some containing multiple mitochondria while others are completely void. Microglial processes that engage in minute-to-minute surveillance typically do not have mitochondria. Moreover, unlike process surveillance, mitochondrial motility does not change with animal anesthesia. Likewise, the processes that acutely chemoattract to a lesion site or initially engage with a neuron undergoing programmed cell death do not contain mitochondria. Rather, microglia mitochondria have a delayed arrival into the responding cell processes. Thus, there is subcellular heterogeneity of mitochondrial partitioning and asymmetry between mitochondrial localization and cell process motility or acute damage responses.
Insights
Microglia, the brain's immune cells, dynamically partition mitochondria within their processes. These energy powerhouses are often absent during surveillance and initial injury responses, arriving later.
Area of Science:
- Neuroscience
- Cell Biology
- Immunology
Background:
- Microglia are essential for brain surveillance and homeostasis.
- Microglial metabolism is crucial, but their mitochondrial dynamics are poorly understood.
- Subcellular partitioning of mitochondria in microglia during brain activity is unknown.
Purpose of the Study:
- To investigate the subcellular localization and dynamic reorganization of mitochondria in microglia within the intact brain.
- To understand how mitochondrial distribution changes during microglial surveillance, injury response, and phagocytosis.
Main Methods:
- Intravital imaging of microglia mitochondria in live animals.
- Observation of microglial process behavior during surveillance and response to stimuli.
Main Results:
- Microglial processes show significant subcellular heterogeneity in mitochondrial content; some are rich, others devoid.
- Surveilling microglial processes typically lack mitochondria, with delayed mitochondrial arrival during acute injury responses.
- Mitochondrial motility in processes remains constant regardless of anesthesia, unlike process extension.
Conclusions:
- Microglia exhibit asymmetric mitochondrial partitioning, with mitochondria not always co-localizing with motile or acutely responding processes.
- This suggests a complex, non-uniform distribution strategy for mitochondria within microglia, potentially optimizing energy supply based on cellular demands.
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