How dysfunctional mitochondria drive T cell exhaustion: (IMAGE)
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Damaged mitochondria in CD8⁺ T cells increase the activity of a protein degrading machine known as the proteasome, which preferentially degrades mitochondrial hemoproteins, releasing “regulatory heme” (RH). Elevated RH travels into the nucleus through the transporter PGRMC2, where it binds to the transcription factor BACH2, inducing its degradation and, consequently, the activation of gene expression programs that push T cells into terminal exhaustion.
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Yingxi Xu
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