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TFAM-Associated Mitochondrial Dynamics and Metabolic Reprogramming Regulate Microglial Polarization: Temporal and

Yuxuan Zhang1, Ximeng Wang2,3, Dachuan Li1

  • 1Department of Orthopedics, Huashan Hospital, Fudan University, Shanghai, Shanghai, China.

FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology
|January 22, 2026
PubMed
Summary
This summary is machine-generated.

Microglial polarization influences neuroinflammation and repair. This study reveals mitochondrial dynamics, regulated by TFAM, impact microglial metabolic reprogramming and polarization, offering new therapeutic targets for neural injuries.

Keywords:
TFAMcell polarizationfatty acid oxidationglycolysismetabolismmicrogliamitochondria

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Area of Science:

  • Neuroscience
  • Cell Biology
  • Metabolic pathways

Background:

  • Microglial polarization is critical for neuroinflammation and tissue repair.
  • Mitochondrial dynamics (fusion/fission) and metabolic reprogramming are implicated in microglial function.
  • The precise relationship between mitochondrial dynamics and microglial polarization requires further elucidation.

Purpose of the Study:

  • To investigate the causal link between mitochondrial dynamics, metabolic reprogramming, and microglial polarization.
  • To explore the role of mitochondrial transcription factor A (TFAM) in regulating these processes.

Main Methods:

  • Utilized mouse microglial cell cultures and animal models.
  • Manipulated mitochondrial fusion using a promoter (M1).
  • Assessed the effects of knocking down TFAM on mitochondrial dynamics and cellular metabolism.

Main Results:

  • Promoting mitochondrial fusion reduced glycolysis and increased fatty acid oxidation, impacting microglial polarization.
  • Knocking down TFAM induced mitochondrial fission, decreased fatty acid oxidation, enhanced glycolysis, and promoted pro-inflammatory M1 microglial polarization.
  • Established a chronological sequence and causal relationships between mitochondrial dynamics, metabolism, and microglial polarization.

Conclusions:

  • TFAM plays a significant role in regulating mitochondrial dynamics in microglia.
  • Mitochondrial dynamics and metabolic reprogramming are key regulators of microglial polarization.
  • Findings provide novel therapeutic targets for neural injuries and neurodegenerative diseases.