Title

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

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