Cited by 1,185Autophagy in Disease and TherapyCell death mechanisms and regulationErythrocyte Function and Pathophysiology

Essential role for Nix in autophagic maturation of erythroid cells

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Sandoval, Hector, Thiagarajan, Perumal, Dasgupta, Swapan K., Schumacher, Armin, Prchal, Josef T., Chen, Min, Wang, Jin·2008·Nature

Abstract

Erythroid cells undergo enucleation and the removal of organelles during terminal differentiation. Although autophagy has been suggested to mediate the elimination of organelles for erythroid maturation, the molecular mechanisms underlying this process remain undefined. Here we report a role for a Bcl-2 family member, Nix (also called Bnip3L), in the regulation of erythroid maturation through mitochondrial autophagy. Nix(-/-) mice developed anaemia with reduced mature erythrocytes and compensatory expansion of erythroid precursors. Erythrocytes in the peripheral blood of Nix(-/-) mice exhibited mitochondrial retention and reduced lifespan in vivo. Although the clearance of ribosomes proceeded normally in the absence of Nix, the entry of mitochondria into autophagosomes for clearance was defective. Deficiency in Nix inhibited the loss of mitochondrial membrane potential (DeltaPsi(m)), and treatment with uncoupling chemicals or a BH3 mimetic induced the loss of DeltaPsi(m) and restored the sequestration of mitochondria into autophagosomes in Nix(-/-) erythroid cells. These results suggest that Nix-dependent loss of DeltaPsi(m) is important for targeting the mitochondria into autophagosomes for clearance during erythroid maturation, and interference with this function impairs erythroid maturation and results in anaemia. Our study may also provide insights into molecular mechanisms underlying mitochondrial quality control involving mitochondrial autophagy.

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Crossref · 10.1038/nature07006

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Authors
Sandoval, H., Thiagarajan, P., Dasgupta, S. K., Schumacher, A., Prchal, J. T., Chen, M., & Wang, J.
Affiliations
  • Baylor College of Medicine (US)
  • University of Utah (US)
Corresponding author
  • Chen, Min
  • Wang, Jin
Venue
Nature
Published
2008-05-04
Volume
454
Issue
7201
Pages
232-235
ISSN
  • 0028-0836 (ISSN-L)
  • 1476-4687
OpenAlex
W2047242847
Cited by
1,185
References
32
Citations by year
2026: 48 · 2025: 57 · 2024: 54 · 2023: 60 · 2022: 82 · 2021: 98 · 2020: 88 · 2019: 70 · 2018: 72 · 2017: 77 · 2016: 56 · 2015: 63 · 2014: 62 · 2013: 57 · 2012: 62
FWCI
43.69
Type
journal article
Language
en
Open access
Locations
  • Nature (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
  • RePEc: Research Papers in Economics (submittedVersion)
Funders
  • National Institute of General Medical Sciences (R01GM087710)
  • National Institute of Allergy and Infectious Diseases (R01AI074949, R01AI056210, F31AI058932)
Topics
  • Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
  • Health Sciences › Medicine › Physiology › Erythrocyte Function and Pathophysiology
Keywords
BNIP3L, Bcl-2 family proteins, erythroid maturation, mitophagy, enucleation, anemia, erythrocyte lifespan, mitochondrial membrane potential, autophagosome formation, mitochondrial quality control, erythroid precursors
MeSH terms
Animals, Autophagy, Biphenyl Compounds, Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone, Cell Survival, Erythropoiesis, Membrane Proteins, Mice, Inbred C57BL, Mitochondria, Nitrophenols, Piperazines, Reticulocytes, Sulfonamides, Apoptosis, Mitochondrial Proteins, Erythroid Cells, Mice, Embryonic Stem Cells

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