Essential role for Nix in autophagic maturation of erythroid cells
Open accessAbstract
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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From The connection between the dynamic remodeling of the mitochondrial network and the regulation of muscle mass (2021) · cites this paper as [140]
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BCL-XL expression is essential for human erythropoiesis and engraftment of hematopoietic stem cells
Afreen, S., Bohler, S., Müller, A., Demmerath, E.-M., Weiss, J. M., Jutzi, J. S., Schachtrup, K., Kunze, M., & Erlacher, M. (2020) · Cell Death & Disease · doi:10.1038/s41419-019-2203-z · Cited by 55 · see citing works
Alternative Macroautophagic Pathways
Juenemann, K., & Reits, E. A. (2012) · International Journal of Cell Biology · doi:10.1155/2012/189794 · Cited by 58 · see citing works
Novel Insights into the Anti-Aging Role of Mitophagy
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Forkhead box O3 (FoxO3) regulates kidney tubular autophagy following urinary tract obstruction
Li, L., Zviti, R., Ha, C., Wang, Z. V., Hill, J. A., & Lin, F. (2017) · Journal of Biological Chemistry · doi:10.1074/jbc.m117.791483 · Cited by 44 · see citing works
The response to DNA damage during differentiation: Pathways and consequences
Fortini, P., Ferretti, C., & Dogliotti, E. (2013) · Mutation Research - Fundamental and Molecular Mechanisms of Mutagenesis · doi:10.1016/j.mrfmmm.2013.03.004 · Cited by 45 · see citing works
- 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
- PMC
- PMC2570948
- 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
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- 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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