A short linear motif in BNIP3L (NIX) mediates mitochondrial clearance in reticulocytes

Zhang, Ji; Loyd, Melanie R.; Randall, Mindy S.; Waddell, M. Brett; Kriwacki, Richard W.; Ney, Paul A.

doi:10.4161/auto.20764

Cited by 76 publications

(83 citation statements)

References 46 publications

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“…This is likely due to a failure of early stage erythrocyte differentiation because the bone marrow Sca1 À c-Kit þ progenitors were severely downregulated (Fig. 7b), as previously reported 22 . Analysis of circulating EC indicated that the population of mitochondria-containing Ter119 þ cells was higher in Atg7 F/F Cre mice and Ulk1 gt/gt mice than in WT mice (Fig.…”

Section: Lc3-ii/lc3-i (Ratio) Rc Ec Eb Wt Dko Rc Ec Eb Rc Ec Eb Rc Ecsupporting

confidence: 77%

“…In contrast, Nix expression levels correlated with mitophagy in all mouse genotypes. Nix was reported to have a function for the partial elimination of mitochondria via conventional macroautophagy [19][20][21] , and also found crucial for LC3-independent mitophagy 22 . The latter machinery may be identical to alternative macroautophagy.…”

Section: Discussionmentioning

confidence: 99%

“…These data confirmed the partial impairment of mitochondrial clearance in Atg5 À / À and severe impairment in Ulk1 gt/gt and DKO EC. The protein Nix was recently identified as a selective autophagy receptor responsible for mitochondrial clearance from reticulocytes [19][20][21][22] . Accordingly, the expression level of Nix in these cell types was proportional to the extent of mitophagy (Fig.…”

Section: Mitochondrial Removal By Alternative Macroautophagy In Vivomentioning

confidence: 99%

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Ulk1-mediated Atg5-independent macroautophagy mediates elimination of mitochondria from embryonic reticulocytes

et al. 2014

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Macroautophagy is a highly conserved intracellular process responsible for the degradation of subcellular constituents. Macroautophagy was recently suggested to be involved in the removal of mitochondria from reticulocytes during the final stage of erythrocyte differentiation. Although Atg5 and Atg7 are indispensable for macroautophagy, their role in mitochondrial clearance remains controversial. We recently discovered that mammalian cells use conventional Atg5/Atg7-dependent macroautophagy as well as an alternative Unc-51-like kinase 1 (Ulk1)-dependent Atg5/Atg7-independent macroautophagy process. We hypothesized that the latter may be involved in mitochondrial clearance from reticulocytes during erythrocyte differentiation. Here we report that fetal definitive reticulocytes from Ulk1-deficient and Ulk1/Atg5 double-deficient mice retain their mitochondria, whereas the mitochondria are engulfed and digested within autophagic structures in wild-type and Atg5-deficient mice. Mitochondrial retention by Ulk1-deficient reticulocytes is far less marked in primitive and adult definitive reticulocytes. These data indicate that Ulk1-dependent Atg5-independent macroautophagy is the dominant process of mitochondrial clearance from fetal definitive reticulocytes.

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Section: Lc3-ii/lc3-i (Ratio) Rc Ec Eb Wt Dko Rc Ec Eb Rc Ec Eb Rc Ecsupporting

confidence: 77%

Section: Discussionmentioning

confidence: 99%

Section: Mitochondrial Removal By Alternative Macroautophagy In Vivomentioning

confidence: 99%

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Ulk1-mediated Atg5-independent macroautophagy mediates elimination of mitochondria from embryonic reticulocytes

et al. 2014

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“…Also, BIM-and PUMA-deficient mice had no defect in clearance, indicating that NIX does not sensitize mitochondria to BH3-only proteinmediated depolarization. Further, BCL-X L is not co-required with NIX [91], nor does it prevent clearance in NIX's absence [74], although there is evidence that it enhances BNIP3-mediated mitochondrial clearance in Hela cells [95]. Finally, Bak disruption is the only genetic mutation to date, shown to suppress the NIX phenotype [74].…”

Section: Role Of Nix In Programmed Mitochondrial Clearance: An Updatementioning

confidence: 95%

“…Additionally, the cytoplasmic domain contains a LIR motif and a novel short linear motif (SLiM). Bioinformatic analysis predicts that the cytoplasmic domain is disordered, but has regions of secondary structure [74]. The LIR is predicted to form a β-strand and the SLiM an α-helix centered on a triplet of hydrophobic amino acids.…”

Section: Bnip3 and Nix: Multifunctional Outer Mitochondrial Membrane mentioning

confidence: 99%

Mitochondrial autophagy: Origins, significance, and role of BNIP3 and NIX

Ney

2015

Biochimica et Biophysica Acta (BBA) - Molecular Cell Research

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Mitochondrial autophagy (mitophagy) is a core cellular activity. In this review, we consider mitophagy and related cellular processes and discuss their significance for human disease. Strong parallels exist between mitophagy and xenophagy employed in host defense. These mechanisms converge on receptors in the innate immune system in clinically relevant scenarios. Mitophagy is part of a cellular quality control mechanism, which is implicated in degenerative disease, especially neurodegenerative disease. Furthermore, mitophagy is an aspect of cellular remodeling, which is employed during development. BNIP3 and NIX are related multi-functional outer mitochondrial membrane proteins. BNIP3 regulates mitophagy during hypoxia, whereas NIX is required for mitophagy during development of the erythroid lineage. Recent advances in the field of BNIP3- and NIX-mediated mitophagy are discussed.

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Mitochondrial clearance: mechanisms and roles in cellular fitness

Onishi

Okamoto

2021

FEBS Letters

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Edited by Agnieszka ChacinskaMitophagy is one of the selective autophagy pathways that catabolizes dysfunctional or superfluous mitochondria. Under mitophagy-inducing conditions, mitochondria are labeled with specific molecular landmarks that recruit the autophagy machinery to the surface of mitochondria, enclosed into autophagosomes, and delivered to lysosomes (vacuoles in yeast) for degradation. As damaged mitochondria are the major sources of reactive oxygen species, mitophagy is critical for mitochondrial quality control and cellular health. Moreover, appropriate control of mitochondrial quantity via mitophagy is vital for the energy supply-demand balance in cells and whole organisms, cell differentiation, and developmental programs. Thus, it seems conceivable that defects in mitophagy could elicit pleiotropic pathologies such as excess inflammation, tissue injury, neurodegeneration, and aging. In this review, we will focus on the molecular basis and physiological relevance of mitophagy, and potential of mitophagy as a therapeutic target to overcome such disorders.

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A short linear motif in BNIP3L (NIX) mediates mitochondrial clearance in reticulocytes

Cited by 76 publications

References 46 publications

Ulk1-mediated Atg5-independent macroautophagy mediates elimination of mitochondria from embryonic reticulocytes

Ulk1-mediated Atg5-independent macroautophagy mediates elimination of mitochondria from embryonic reticulocytes

Mitochondrial autophagy: Origins, significance, and role of BNIP3 and NIX

Mitochondrial clearance: mechanisms and roles in cellular fitness

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