Nature Immunology, Published online: 22 November 2021; doi:10.1038/s41590-021-01070-5

Mitochondria regulate endoplasmic reticulum (ER) size and protein maturation in healthy cells by releasing aspartate, regenerating cytoplasmic NAD+ and ADP-ribosylating the ER stress sensor BiP. In the autoimmune disease rheumatoid arthritis, a deficiency in mitochondrial aspartate in T cells causes an increase in ER size and excess production of the inflammatory mediator tumor necrosis factor (TNF), driving tissue inflammation.