Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Comment
. 2021 Nov;22(11):1354-1355.
doi: 10.1038/s41590-021-01050-9.

Mitochondrial dysfunction in the erythroid compartment

Mariana J Kaplan  1
Affiliations
Comment

Mitochondrial dysfunction in the erythroid compartment

Mariana J Kaplan. Nat Immunol. 2021 Nov.

Abstract

Erythroid mitochondrial retention, a feature associated with impairments in the ubiquitin-proteasome system, is detected in a subset of pediatric lupus patients and is associated with the type I Interferon pathway.

PubMed Disclaimer

Figures

Figure 1
Figure 1. Deficient mitochondrial removal and association with type I interferon responses.
Defective HIF-2α degradation impairs UPS activation and mitophagy. A percentage of patients with childhood onset SLE display dysregulated erythropoiesis characterized by deficient mitophagy, in association with abnormal regulation of HIF. Mitochondria containing RBCs, when opsonized by antibodies and then engulfed by macrophages, activate the cGAS-STING pathway leading to increased type I IFN synthesis.
See this image and copyright information in PMC

Comment on

References

    1. Casey KA, Smith MA, Sinibaldi D, Seto NL, Playford MP, Wang X, et al. Modulation of Cardiometabolic Disease Markers by Type I Interferon Inhibition in Systemic Lupus Erythematosus. Arthritis Rheumatol. 73, 459–471 (2021). - PMC - PubMed
    1. Kim J, Gupta R, Blanco LP, Yang S, Shteinfer-Kuzmine A, Wang K, et al. VDAC oligomers form mitochondrial pores to release mtDNA fragments and promote lupus-like disease. Science 366, 1531–1536 (2019). - PMC - PubMed
    1. Rai P, Janardhan KS, Meacham J, Madenspacher JH, Lin WC, Karmaus PWF, et al. IRGM1 links mitochondrial quality control to autoimmunity. Nat. Immunol 22, 312–321 (2021). - PMC - PubMed
    1. Lood C, Blanco LP, Purmalek MM, Carmona-Rivera C, De Ravin SS, Smith CK, et al. Neutrophil extracellular traps enriched in oxidized mitochondrial DNA are interferogenic and contribute to lupus-like disease. Nat. Med 22, 146–153 (2016). - PMC - PubMed
    1. Caza TN, Fernandez DR, Talaber G, Oaks Z, Haas M, Madaio MP, et al. HRES-1/Rab4-mediated depletion of Drp1 impairs mitochondrial homeostasis and represents a target for treatment in SLE. Ann. Rheum. Dis 73, 1888–1897 (2014). - PMC - PubMed

MeSH terms