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Comment
. 2021 Dec;22(12):1474-1476.
doi: 10.1038/s41590-021-01069-y.

Shortage of aspartate in mitochondria fuels arthritis

Marc Scherlinger  1   2   3 , George C Tsokos  4
Affiliations
Comment

Shortage of aspartate in mitochondria fuels arthritis

Marc Scherlinger et al. Nat Immunol. 2021 Dec.

Abstract

In patients with rheumatoid arthritis, a short supply of aspartate in the mitochondria can force the endoplasmic reticulum of T cells to generate transmembrane TNF, which in turn contributes to synovial inflammation.

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Conflict of interest statement

Competing interests

The authors declare no competing interests

Figures

Figure 1
Figure 1. In RA a deficient aspartate shuttle from dysfunctional mitochondria drives TNF synthesis in T cells.
In T cells, aspartate is produced in the mitochondria from the tricarboxylic acid (TCA) cycle and shuttles to the cytosol to regenerate the electron acceptor nicotinamide adenine dinucleotide (NAD). NAD is a cofactor for ADP-ribosylation of proteins such as the chaperone protein BiP. However, in T cells from patients with RA a defective aspartate shuttle is responsible for reduced cytosolic NAD+ levels leading to a lack of BiP ADP-ribosylation. Under these conditions, BiP releases the endoplasmic reticulum (ER) stress protein IREα, which promotes ER expansion and the release of large quantities of TNF into the synovial tissue.
See this image and copyright information in PMC

Comment on

References

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