Erythroid mitochondrial retention triggers myeloid-dependent type I interferon in human SLE.
Cell 2021 Aug 19; 184(17):4464-4479.e19
Emerging evidence supports that mitochondrial dysfunction contributes to systemic lupus erythematosus (SLE) pathogenesis. Here we show that programmed mitochondrial removal, a hallmark of mammalian erythropoiesis, is defective in SLE. Specifically, we demonstrate that during human erythroid cell maturation, a hypoxia-inducible factor (HIF)-mediated metabolic switch is responsible for the activation of the ubiquitin-proteasome system (UPS), which precedes and is necessary for the autophagic removal of mitochondria. A defect in this pathway leads to accumulation of red blood cells (RBCs) carrying mitochondria (Mito
Caielli, Simone; Cardenas, Jacob; de Jesus, Adriana Almeida; Baisch, Jeanine; Walters, Lynnette; Blanck, Jean Philippe; Balasubramanian, Preetha; Stagnar, Cristy; Ohouo, Marina; Hong, Seunghee; Nassi, Lorien; Stewart, Katie; Fuller, Julie; Gu, Jinghua; Banchereau, Jacques; Wright, Tracey; Goldbach-Mansky, Raphaela; and Pascual, Virginia, "Erythroid mitochondrial retention triggers myeloid-dependent type I interferon in human SLE." (2021). Faculty Research 2021. 170.