Mitochondria and lysosomes in T cell immunometabolism

Trends Immunol. 2025 Sep;46(9):635-651. doi: 10.1016/j.it.2025.07.014. Epub 2025 Aug 22.

Abstract

Metabolic reprogramming and signaling are key orchestrators of T cell immunity. Recent studies have illustrated important roles for intracellular organelles, especially mitochondria and lysosomes, in enforcing T cell metabolism and signaling in response to various extracellular cues. As such, mitochondrial and lysosomal function contributes to adaptive immunity by regulating T cell activation, differentiation, and functional adaptation. In this Review, we discuss how the interplay between organelle biology and metabolism instructs T cell-mediated immunity, with a particular focus on mitochondria and lysosomes. We also summarize how mitochondria and lysosomes, or their crosstalk with other organelles, orchestrate downstream signaling processes and functional reprogramming of T cells. We conclude with a discussion of the pathophysiological outcomes associated with dysregulation of these organelles.

Keywords: T cells; immunometabolism; lysosomes; metabolic signaling; mitochondria; organelle crosstalk.

Publication types

  • Review

MeSH terms

  • Animals
  • Humans
  • Lymphocyte Activation
  • Lysosomes* / immunology
  • Lysosomes* / metabolism
  • Mitochondria* / immunology
  • Mitochondria* / metabolism
  • Signal Transduction
  • T-Lymphocytes* / immunology
  • T-Lymphocytes* / metabolism