Publication Date:
2008-05-06
Description:
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.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2570948/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉 〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2570948/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sandoval, Hector -- Thiagarajan, Perumal -- Dasgupta, Swapan K -- Schumacher, Armin -- Prchal, Josef T -- Chen, Min -- Wang, Jin -- F31 AI058932/AI/NIAID NIH HHS/ -- R01 AI056210/AI/NIAID NIH HHS/ -- R01 AI056210-05/AI/NIAID NIH HHS/ -- R01 AI074949/AI/NIAID NIH HHS/ -- R01 AI074949-01/AI/NIAID NIH HHS/ -- R01 GM087710/GM/NIGMS NIH HHS/ -- England -- Nature. 2008 Jul 10;454(7201):232-5. doi: 10.1038/nature07006. Epub 2008 May 4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Immunology, Baylor College of Medicine, Houston, Texas 77030, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18454133" target="_blank"〉PubMed〈/a〉
Keywords:
Animals
;
Apoptosis/drug effects
;
*Autophagy/drug effects
;
Biphenyl Compounds/pharmacology
;
Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone/pharmacology
;
Cell Survival/drug effects
;
Embryonic Stem Cells/cytology/drug effects
;
Erythroid Cells/*cytology/drug effects/*metabolism
;
*Erythropoiesis/drug effects
;
Membrane Proteins/deficiency/genetics/*metabolism
;
Mice
;
Mice, Inbred C57BL
;
Mitochondria/drug effects/metabolism/pathology
;
Mitochondrial Proteins/deficiency/genetics/*metabolism
;
Nitrophenols/pharmacology
;
Piperazines/pharmacology
;
Reticulocytes/cytology/drug effects/metabolism
;
Sulfonamides/pharmacology
Print ISSN:
0028-0836
Electronic ISSN:
1476-4687
Topics:
Biology
,
Chemistry and Pharmacology
,
Medicine
,
Natural Sciences in General
,
Physics
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