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T Cell Types and Functions01:24

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Updated: Apr 5, 2026

Multicolor Flow Cytometry-based Quantification of Mitochondria and Lysosomes in T Cells
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Mitochondrial Respiration Controls Lysosomal Function during Inflammatory T Cell Responses.

Francesc Baixauli1, Rebeca Acín-Pérez2, Carolina Villarroya-Beltrí1

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Summary

Mitochondrial dysfunction in T cells impairs lysosome function, leading to inflammation. Restoring NAD+ levels can correct these defects, offering a potential treatment for mitochondrial-related diseases.

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Area of Science:

  • Cellular Biology
  • Immunology
  • Mitochondrial Biology

Background:

  • The endolysosomal system is vital for cellular homeostasis.
  • The regulation of endolysosomal compartments by mitochondrial function is not well understood.

Purpose of the Study:

  • To investigate the impact of mitochondrial dysfunction on T cell function and endolysosomal pathways.
  • To explore potential therapeutic strategies for mitochondrial-related disorders.

Main Methods:

  • Generated a mouse model with defective mitochondrial function in CD4(+) T lymphocytes by deleting the mitochondrial transcription factor A (Tfam).
  • Assessed lysosome function, molecular accumulation (p62, sphingomyelin), endolysosomal trafficking, and autophagy.
  • Evaluated T cell differentiation and in vivo inflammatory responses.
  • Investigated the effect of NAD+ restoration on cellular and inflammatory defects.

Main Results:

  • Mitochondrial respiration deficiency in Tfam-deficient T cells impaired lysosome function, causing p62 and sphingomyelin accumulation.
  • Disrupted endolysosomal trafficking and autophagy were observed, linking mitochondrial defects to lysosomal storage disorders.
  • Impaired lysosome function promoted pro-inflammatory T cell differentiation and exacerbated in vivo inflammation.
  • Restoration of NAD+ levels improved lysosome function and corrected inflammatory defects in Tfam-deficient T cells.

Conclusions:

  • Mitochondria critically regulate lysosome function to maintain T cell differentiation and effector functions.
  • Mitochondrial dysfunction in T cells can lead to lysosomal storage disorders and inflammation.
  • Restoring NAD+ levels presents a potential therapeutic strategy for mitochondrial-related diseases.