Erythroid mitochondrial retention triggers myeloid-dependent type I interferon in human SLE.
Document Type
Article
Publication Date
8-19-2021
Publication Title
Cell
Keywords
JGM
JAX Source
Cell 2021 Aug 19; 184(17):4464-4479.e19
Volume
184
Issue
17
First Page
4464
Last Page
4479
ISSN
1097-4172
PMID
34384544
DOI
https://doi.org/10.1016/j.cell.2021.07.021
Grant
AR070594
Abstract
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
Recommended Citation
Caielli S,
Cardenas J,
de Jesus A,
Baisch J,
Walters L,
Blanck J,
Balasubramanian P,
Stagnar C,
Ohouo M,
Hong S,
Nassi L,
Stewart K,
Fuller J,
Gu J,
Banchereau J,
Wright T,
Goldbach-Mansky R,
Pascual V.
Erythroid mitochondrial retention triggers myeloid-dependent type I interferon in human SLE. Cell 2021 Aug 19; 184(17):4464-4479.e19