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Nix is a selective autophagy receptor for mitochondrial clearance
Open accessAbstract
Autophagy is the cellular homeostatic pathway that delivers large cytosolic materials for degradation in the lysosome. Recent evidence indicates that autophagy mediates selective removal of protein aggregates, organelles and microbes in cells. Yet, the specificity in targeting a particular substrate to the autophagy pathway remains poorly understood. Here, we show that the mitochondrial protein Nix is a selective autophagy receptor by binding to LC3/GABARAP proteins, ubiquitin-like modifiers that are required for the growth of autophagosomal membranes. In cultured cells, Nix recruits GABARAP-L1 to damaged mitochondria through its amino-terminal LC3-interacting region. Furthermore, ablation of the Nix:LC3/GABARAP interaction retards mitochondrial clearance in maturing murine reticulocytes. Thus, Nix functions as an autophagy receptor, which mediates mitochondrial clearance after mitochondrial damage and during erythrocyte differentiation.
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“Mitophagy can also occur through Parkin-independent pathways.”
From Mitochondrial Dynamics and Mitophagy in Skeletal Muscle Health and Aging (2021) · cites this paper as [140]
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Cites
Pankiv, S., Clausen, T. H., Lamark, T., Brech, A., Bruun, J.-A., Outzen, H., Øvervatn, A., Bjørkøy, G., & Johansen, T. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m702824200 · Cited by 4,578
Parkin is recruited selectively to impaired mitochondria and promotes their autophagy
Narendra, D., Tanaka, A., Suen, D.-F., & Youle, R. J. (2008) · The Journal of Cell Biology · doi:10.1083/jcb.200809125 · Cited by 4,026
Autophagosome formation: core machinery and adaptations
Xie, Z., & Klionsky, D. J. (2007) · Nature Cell Biology · doi:10.1038/ncb1007-1102 · Cited by 2,237
Homeostatic levels of p62 control cytoplasmic inclusion body formation in autophagy-deficient mice.
Komatsu, M., Waguri, S., Koike, M., Sou, Y.-S., Ueno, T., Hara, T., Mizushima, N., Iwata, J.-I., Ezaki, J., Murata, S., et al. (2007) · Cell · doi:10.1016/j.cell.2007.10.035 · Cited by 2,124
Dynamics and diversity in autophagy mechanisms: lessons from yeast
Nakatogawa, H., Suzuki, K., Kamada, Y., & Ohsumi, Y. (2009) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2708 · Cited by 1,761
Selective degradation of mitochondria by mitophagy
Kim, I., Rodriguez-Enriquez, S., & Lemasters, J. J. (2007) · Archives of Biochemistry and Biophysics · doi:10.1016/j.abb.2007.03.034 · Cited by 1,558
Bellot, G., Garcia-Medina, R., Gounon, P., Chiche, J., Roux, D., Pouysségur, J., & Mazure, N. M. (2009) · Molecular and Cellular Biology · doi:10.1128/mcb.00166-09 · Cited by 1,501
A Role for Ubiquitin in Selective Autophagy
Kirkin, V., McEwan, D. G., Novak, I., & Đikić, I. (2009) · Molecular Cell · doi:10.1016/j.molcel.2009.04.026 · Cited by 1,268
Essential role for Nix in autophagic maturation of erythroid cells
Sandoval, H., Thiagarajan, P., Dasgupta, S. K., Schumacher, A., Prchal, J. T., Chen, M., & Wang, J. (2008) · Nature · doi:10.1038/nature07006 · Cited by 1,185
A Role for NBR1 in Autophagosomal Degradation of Ubiquitinated Substrates
Kirkin, V., Lamark, T., Sou, Y.-S., Bjørkøy, G., Nunn, J. L., Bruun, J.-A., Shvets, E., McEwan, D. G., Clausen, T. H., Wild, P., et al. (2009) · Molecular Cell · doi:10.1016/j.molcel.2009.01.020 · Cited by 1,065
Cited by
Sorted by citations
Autophagy: Renovation of Cells and Tissues
Mizushima, N., & Komatsu, M. (2011) · Cell · doi:10.1016/j.cell.2011.10.026 · Cited by 6,615
“The role of other mitochondrial adaptor proteins such as Nix remains unknown (Novak et al., 2010).”
BackgroundGuidelines for the use and interpretation of assays for monitoring autophagy (3rd edition).
Klionsky, D. J., Abdelmohsen, K., Abe, A., Abedin, M. J., Abeliovich, H., Acevedo Arozena, A., Adachi, H., Adams, C. M., Adams, P. D., Adeli, K., et al. (2016) · Autophagy · doi:10.1080/15548627.2015.1100356 · Cited by 5,894
“NIX are highly dependent on GABARAP and less dependent on LC3 proteins.(210,211) Furthermore, commercial antibodies for GABARAPL1 also recognize GABARAP,(138,143) which might lead to misinterpretation of experiments, in particular those”
Guidelines for the use and interpretation of assays for monitoring autophagy
Klionsky, D. J., Abdalla, F. C., Abeliovich, H., Abraham, R. T., Acevedo-Arozena, A., Adeli, K., Agholme, L., Agnello, M., Agostinis, P., Aguirre-Ghiso, J. A., et al. (2012) · Autophagy · doi:10.4161/auto.19496 · Cited by 3,996
“Certain types of mitophagy induced by BNIP3L/NIX are highly dependent on GABARAP and less dependent on LC3 proteins.(147) Furthermore, commercial antibodies for GABARAPL1 also recognize GABARAP,(108) which might lead to misinterpretation of experiments, in particular those using immunohistochemical techniques.”
BackgroundAutophagy and the Integrated Stress Response
Kroemer, G., Mariño, G., & Levine, B. (2010) · Molecular Cell · doi:10.1016/j.molcel.2010.09.023 · Cited by 3,506
“, 2009) as well as BNIP3L (also known as NIX), which binds to mitochondrial membranes (Novak et al., 2010).”
InfluentialYoule, R. J., & Narendra, D. P. (2011) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3028 · Cited by 3,273
“NIX is localized to the OMM and contains a WXXL-like motif facing the cytosol, which binds the mammalian Atg8 orthologue, LC3, and the LC3 homologue, GABA receptor-associated protein (GABARAP), in vitro and in vivo”
BackgroundThe Role of Atg Proteins in Autophagosome Formation
Mizushima, N., Yoshimori, T., & Ohsumi, Y. (2011) · Annual Review of Cell and Developmental Biology · doi:10.1146/annurev-cellbio-092910-154005 · Cited by 2,978
Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition) 1
Klionsky, D. J., Abdel-Aziz, A. K., Abdelfatah, S., Abdellatif, M., Abdoli, A., Abel, S., Abeliovich, H., Abildgaard, M. H., Abudu, Y. P., Acevedo-Arozena, A., et al. (2021) · Autophagy · doi:10.1080/15548627.2020.1797280 · Cited by 2,897
Self-citationOxidative stress and autophagy: The clash between damage and metabolic needs
Filomeni, G., De Zio, D., & Cecconi, F. (2015) · Cell Death & Differentiation · doi:10.1038/cdd.2014.150 · Cited by 2,195
The machinery of macroautophagy
Feng, Y., He, D., Yao, Z., & Klionsky, D. J. (2014) · Cell Research · doi:10.1038/cr.2013.168 · Cited by 2,083
Mitophagy and Quality Control Mechanisms in Mitochondrial Maintenance
Pickles, S., Vigié, P., & Youle, R. J. (2018) · Current Biology · doi:10.1016/j.cub.2018.01.004 · Cited by 2,081
The pathways of mitophagy for quality control and clearance of mitochondria
Ashrafi, G., & Schwarz, T. L. (2013) · Cell Death & Differentiation · doi:10.1038/cdd.2012.81 · Cited by 1,900
“induced mitophagy, as CCCP treatment enhances Nix and LC3 interaction in HeLa cells.(92,93) There is not yet consensus”
BackgroundSelective autophagy mediated by autophagic adapter proteins
Johansen, T., & Lamark, T. (2011) · Autophagy · doi:10.4161/auto.7.3.14487 · Cited by 1,788
Regulation of Mammalian Autophagy in Physiology and Pathophysiology
Ravikumar, B., Sarkar, S., Davies, J. E., Futter, M., García-Arencibia, M., Green-Thompson, Z. W., Jiménez-Sánchez, M., Korolchuk, V. I., Lichtenberg, M., Luo, S., et al. (2010) · Physiological Reviews · doi:10.1152/physrev.00030.2009 · Cited by 1,789
Mitochondrial outer-membrane protein FUNDC1 mediates hypoxia-induced mitophagy in mammalian cells
Liu, L., Feng, D., Chen, G., Chen, M., Zheng, Q., Song, P., Ma, Q., Zhu, C., Wang, R., Qi, W., et al. (2012) · Nature Cell Biology · doi:10.1038/ncb2422 · Cited by 1,738
“(c) HeLa cells were transfected with (Flag)N-Fundc1(1-155)-C(Myc) or (Flag)N-Fundc1(1-139)C(Myc) vectors, respectively.”
MethodMolecular definitions of autophagy and related processes
Galluzzi, L., Baehrecke, E. H., Ballabio, A., Boya, P., Bravo‐San Pedro, J. M., Cecconi, F., Choi, A. M., Chu, C. T., Codogno, P., Colombo, M. I., et al. (2017) · The EMBO Journal · doi:10.15252/embj.201796697 · Cited by 1,646
Network organization of the human autophagy system
Behrends, C., Sowa, M. E., Gygi, S. P., & Harper, J. W. (2010) · Nature · doi:10.1038/nature09204 · Cited by 1,554
Autophagy in mammalian development and differentiation
Mizushima, N., & Levine, B. (2010) · Nature Cell Biology · doi:10.1038/ncb0910-823 · Cited by 1,555
“Nix is required for the selective removal of mitochondria but not that of ribosomes or nuclei; in Nix −/− reticulocytes, autophagosomes are generated but there is a deficiency in the loss of the mitochondrial membrane potential and consequent mitochondrial engulfment by autophagosome”
BackgroundMechanisms regulating skeletal muscle growth and atrophy
Schiaffino, S., Dyar, K. A., Ciciliot, S., Blaauw, B., & Sandri, M. (2013) · The FEBS Journal · doi:10.1111/febs.12253 · Cited by 1,492
Mechanisms of mitophagy in cellular homeostasis, physiology and pathology
Palikaras, K., Lionaki, E., & Tavernarakis, N. (2018) · Nature Cell Biology · doi:10.1038/s41556-018-0176-2 · Cited by 1,556
Autophagy, mitochondria and oxidative stress: cross-talk and redox signalling.
Lee, J., Giordano, S., & Zhang, J. (2012) · Biochemical Journal · doi:10.1042/bj20111451 · Cited by 1,438
Self-citationMolecular mechanisms and physiological functions of mitophagy
Onishi, M., Yamano, K., Sato, M., Matsuda, N., & Okamoto, K. (2021) · The EMBO Journal · doi:10.15252/embj.2020104705 · Cited by 1,469
“In CCCP-treated cells, NIX recruits GABARAP-L1 to damaged mitochondria and promotes mitophagy in a manner dependent on its LIR motif (Novak et al , 2010).”
Mitochondrial energetics in the kidney
Bhargava, P., & Schnellmann, R. G. (2017) · Nature Reviews Nephrology · doi:10.1038/nrneph.2017.107 · Cited by 1,391
The autophagosome: origins unknown, biogenesis complex
Lamb, C. A., Yoshimori, T., & Tooze, S. A. (2013) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3696 · Cited by 1,367
Phosphorylation of the Autophagy Receptor Optineurin Restricts Salmonella Growth
Wild, P., Farhan, H., McEwan, D. G., Wagner, S., Rogov, V. V., Brady, N. R., Richter, B., Korac, J., Waidmann, O., Choudhary, C., et al. (2011) · Science · doi:10.1126/science.1205405 · Cited by 1,298
Cellular and molecular mechanisms of muscle atrophy
Bonaldo, P., & Sandri, M. (2013) · Disease Models & Mechanisms · doi:10.1242/dmm.010389 · Cited by 1,284
“Indeed, patients chronically treated with bortezomib, a proteasome inhibitor that was approved by the FDA to treat multiple myeloma, display cardiac complications (Orciuolo et al., 2007).”
Mitochondria and the Autophagy–Inflammation–Cell Death Axis in Organismal Aging
Green, D. R., Galluzzi, L., & Kroemer, G. (2011) · Science · doi:10.1126/science.1201940 · Cited by 1,245
Regulation of autophagy by ROS: physiology and pathology
Scherz-Shouval, R., & Elazar, Z. (2011) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2010.07.007 · Cited by 1,263
Cellular quality control by the ubiquitin–proteasome system and autophagy
Pohl, C., & Dikic, I. (2019) · Science · doi:10.1126/science.aax3769 · Cited by 1,212
Cargo recognition and trafficking in selective autophagy
Stolz, A., Ernst, A., & Dikic, I. (2014) · Nature Cell Biology · doi:10.1038/ncb2979 · Cited by 1,207
Cargo recognition and degradation by selective autophagy
Gatica, D., Lahiri, V., & Klionsky, D. J. (2018) · Nature Cell Biology · doi:10.1038/s41556-018-0037-z · Cited by 1,067
Chu, C. T., Ji, J., Dagda, R. K., Jiang, J. F., Tyurina, Y. Y., Kapralov, A. A., Tyurin, V. A., Yanamala, N., Shrivastava, I. H., Mohammadyani, D., et al. (2013) · Nature Cell Biology · doi:10.1038/ncb2837 · Cited by 1,083
Mitochondrial dynamics and inheritance during cell division, development and disease
Mishra, P., & Chan, D. C. (2014) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3877 · Cited by 1,076
Mitophagy: mechanisms, pathophysiological roles, and analysis
Ding, W.-X., & Yin, X.-M. (2012) · bchm · doi:10.1515/hsz-2012-0119 · Cited by 1,032
The mechanisms and roles of selective autophagy in mammals
Vargas, J. N. S., Hamasaki, M., Kawabata, T., Youle, R. J., & Yoshimori, T. (2022) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-022-00542-2 · Cited by 1,088
Rogov, V., Dötsch, V., Johansen, T., & Kirkin, V. (2014) · Molecular Cell · doi:10.1016/j.molcel.2013.12.014 · Cited by 992
Autophagy at the crossroads of catabolism and anabolism
Kaur, J., & Debnath, J. (2015) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm4024 · Cited by 1,036
Mitochondrial dynamics and mitochondrial quality control
Ni, H.-M., Williams, J. A., & Ding, W.-X. (2015) · Redox Biology · doi:10.1016/j.redox.2014.11.006 · Cited by 931
“Prevention of cardiolipin translocation to the outer mitochondrial surface inhibited GFP-LC3 co-localization with mitochondria and mitophagy [82].”
BackgroundThe mitophagy pathway and its implications in human diseases
Wang, S., Long, H., Hou, L., Feng, B., Ma, Z., Wu, Y., Zeng, Y., Cai, J., Zhang, D., & Zhao, G. (2023) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-023-01503-7 · Cited by 991
“104,105 The signi fi cance of NIX in mitophagy was fi rstly demonstrated in the generation of mature erythrocytes.”
BackgroundPrinciples and Current Strategies for Targeting Autophagy for Cancer Treatment
Amaravadi, R. K., Lippincott‐Schwartz, J., Yin, X., Weiss, W. A., Takebe, N., Timmer, W. C., DiPaola, R. S., Lotze, M. T., & White, E. (2011) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-10-2634 · Cited by 912
“The cargo adaptor protein NIX similarly recruits mitochondria to LC3-containing membranes (25).”
BackgroundThe LIR motif – crucial for selective autophagy
Birgisdottir, Å. B., Lamark, T., & Johansen, T. (2013) · Journal of Cell Science · doi:10.1242/jcs.126128 · Cited by 914
“However, in contrast to Bnip3, Nix does not interact with J o u rn a l o f C e ll S c ie n c e LC3B but with GABARAP-L1 during mitochondrial stress (Schwarten et al., 2009; Novak et al., 2010).”
BackgroundInfluentialCompromised autophagy and neurodegenerative diseases
Menzies, F. M., Fleming, A., & Rubinsztein, D. C. (2015) · Nature Reviews Neuroscience · doi:10.1038/nrn3961 · Cited by 851
Recent insights into the function of autophagy in cancerPreprint
Amaravadi, R. K., Kimmelman, A. C., & White, E. (2016) · Genes & Development · doi:10.1101/gad.287524.116 · Cited by 828
“These mitophagy adaptors interact directlywith processed LC3 and promote an overall reduction in mitochondrial mass as an adaptive response to stresses (Novak et al. 2010; Hanna et al. 2012; Liu et al. 2012; Chourasia et al. 2015a).”
BackgroundUbiquitination and selective autophagy
Shaid, S., Brandts, C. H., Serve, H., & Dikic, I. (2013) · Cell Death & Differentiation · doi:10.1038/cdd.2012.72 · Cited by 800
“reported to promote Parkin translocation and Parkin-mediated mitophagy in mouse embryonic fibroblast(85) and can recruit GABARAPL1 to depolarised mitochondria.(71) Another mitochondrial membrane protein FUN14 domain containing 1”
BackgroundKubli, D. A., & Gustafsson, Å. B. (2012) · Circulation Research · doi:10.1161/circresaha.112.265819 · Cited by 825
“In mammalian cells, mitochondrial NIX/BNIP3L and BNIP3 have been identified as autophagy receptors for the selective clearance of mitochondria in cells.(9,117,118) We have found that BNIP3 promotes mitophagy in cells including cardiac myocytes.”
BackgroundNarendra, D. P., Kane, L. A., Hauser, D. N., Fearnley, I. M., & Youle, R. J. (2010) · Autophagy · doi:10.4161/auto.6.8.13426 · Cited by 810
Weidberg, H., Shvets, E., Shpilka, T., Shimron, F., Shinder, V., & Elazar, Z. (2010) · The EMBO Journal · doi:10.1038/emboj.2010.74 · Cited by 777
“The GATE-16/ GABARAP subfamily, previously implicated in intra-cellular protein trafficking processes (Sagiv et al, 2000; Kittler et al, 2001; Nakamura et al, 2008), was recently linked to auto- phagy (Betin and Lane, 2009; Novak et al, 2010).”
BackgroundHanna, R. A., Quinsay, M. N., Orogo, A. M., Giang, K., Rikka, S., & Gustafsson, Å. B. (2012) · Journal of Biological Chemistry · doi:10.1074/jbc.m111.322933 · Cited by 762
“(23) that reported that disrupting the interaction betweenNix and LC3A or GABARAP caused only a partial reduction in mitochondrial clearance.”
BackgroundInfluentialRegulation of selective autophagy: the p62/SQSTM1 paradigm
Lamark, T., Svenning, S., & Johansen, T. (2017) · Essays in Biochemistry · doi:10.1042/ebc20170035 · Cited by 753
Selective Autophagy: ATG8 Family Proteins, LIR Motifs and Cargo Receptors
Johansen, T., & Lamark, T. (2019) · Journal of Molecular Biology · doi:10.1016/j.jmb.2019.07.016 · Cited by 736
Ubiquitin-Dependent And Independent Signals In Selective Autophagy
Khaminets, A., Behl, C., & Đikić, I. (2015) · Trends in Cell Biology · doi:10.1016/j.tcb.2015.08.010 · Cited by 750
Cellular mitophagy: Mechanism, roles in diseases and small molecule pharmacological regulation
Lü, Y., Li, Z., Zhang, S., Zhang, T., Liu, Y., & Zhang, L. (2023) · Theranostics · doi:10.7150/thno.79876 · Cited by 738
“The NIX protein can directly bind to LC3 through its BH3 domain and induce mitophagy [37].”
BackgroundProtein breakdown in muscle wasting: Role of autophagy-lysosome and ubiquitin-proteasome
Sandri, M. (2013) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/j.biocel.2013.04.023 · Cited by 689
Building and decoding ubiquitin chains for mitophagy
Harper, J. W., Ordureau, A., & Heo, J. (2018) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm.2017.129 · Cited by 689
LC3/GABARAP family proteins: autophagy‐(un)related functions
Schaaf, M. B. E., Keulers, T. G., Vooijs, M., & Rouschop, K. M. A. (2016) · The FASEB Journal · doi:10.1096/fj.201600698r · Cited by 665
Nguyen, T. N., Padman, B. S., Usher, J., Oorschot, V., Ramm, G., & Lazarou, M. (2016) · Journal of Cell Biology · doi:10.1083/jcb.201607039 · Cited by 668
“Mutation of the LIR motif in autophagy receptors ablates LC3/GAB ARAP recruitment and blocks selective autophagy (Pankiv et al., 2007; Kirkin et al., 2009; Novak et al., 2010; von Muhlinen et al., 2012).”
BackgroundSelective autophagy: ubiquitin-mediated recognition and beyond
Kraft, C., Peter, M., & Hofmann, K. (2010) · Nature Cell Biology · doi:10.1038/ncb0910-836 · Cited by 639
“The only exception so far is the recently described mitophagy receptor Nix/BNIP3L (BCL2/adenovirus E1B 19-kDa protein-interacting protein 3-like”
BackgroundMitochondria in health, disease, and aging
Harrington, J. S., Ryter, S. W., Plataki, M. E., Price, D. R., & Choi, A. M. K. (2023) · Physiological Reviews · doi:10.1152/physrev.00058.2021 · Cited by 641
Chen, G., Han, Z., Feng, D., Chen, Y., Chen, L., Wu, H., Huang, L., Zhou, C., Cai, X., Fu, C., et al. (2014) · Molecular Cell · doi:10.1016/j.molcel.2014.02.034 · Cited by 615
“, 2009), NIX/BNIP3L (Novak et al., 2010; Sandoval et al., 2008) for red blood cell maturation, and BNIP3 (Hanna et al.”
BackgroundMitophagy, Mitochondrial Homeostasis, and Cell Fate
Ma, K., Chen, G., Li, W., Kepp, O., Zhu, Y., & Chen, Q. (2020) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2020.00467 · Cited by 623
“Several mitophagy receptors including BNIP3, NIX, and BCL2L13 belong to the BCL2 family (Novak et al., 2010; Hanna et al., 2012; Murakawa et al., 2015), highlighting an intrinsic link of mitophagy with apoptosis.”
BackgroundMitochondrial fission and remodelling contributes to muscle atrophy
Romanello, V., Guadagnin, E., Gomes, L., Roder, I., Sandri, C., Petersen, Y., Milan, G., Masiero, E., Del Piccolo, P., Foretz, M., et al. (2010) · The EMBO Journal · doi:10.1038/emboj.2010.60 · Cited by 596
“Recent observations show that Bnip3l recruits the autophagy machinery on mitochondria by binding the lipidated LC3 and Gabarap at the LIR domain (Novak et al, 2010).”
BackgroundMechanisms of Selective Autophagy
Zaffagnini, G., & Martens, S. (2016) · Journal of Molecular Biology · doi:10.1016/j.jmb.2016.02.004 · Cited by 636
“However, some non-canonical LIR motifs, which do not apparently match this consensus, are also found [30,84,85].”
Mitophagy receptor FUNDC1 regulates mitochondrial dynamics and mitophagy
Chen, M., Chen, Z., Wang, Y., Tan, Z. L., Zhu, C., Li, Y., Han, Z., Chen, L., Gao, R., Liu, L., et al. (2016) · Autophagy · doi:10.1080/15548627.2016.1151580 · Cited by 617
Ding, W.-X., Ni, H.-M., Li, M., Liao, Y., Chen, X., Stolz, D. B., Dorn, G. W., & Yin, X.-M. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m110.119537 · Cited by 551
ULK1 translocates to mitochondria and phosphorylates FUNDC1 to regulate mitophagy
Wu, W., Tian, W., Hu, Z., Chen, G., Huang, L., Li, W., Zhang, X., Xue, P., Zhou, C., Liu, L., et al. (2014) · The EMBO Reports · doi:10.1002/embr.201438501 · Cited by 574
“Mitophagy is a major mechanism for mitochondrial quality control at the organelle level through two main mitophagy pathways, involving Parkin/FCCP or mitophagy receptors [2–7].”
Bacteria–autophagy interplay: a battle for survival
Huang, J., & Brumell, J. H. (2014) · Nature Reviews Microbiology · doi:10.1038/nrmicro3160 · Cited by 590
“In mammalian cells, cargo-specific receptors usually contain an LC3-interacting region (LIR) that mediates the recruitment of LC3-decorated autophagosomes to the cargo (for example, mitochondria) [47] [48] [49] .”
BackgroundCleaning house: selective autophagy of organelles
Anding, A. L., & Baehrecke, E. H. (2017) · Developmental Cell · doi:10.1016/j.devcel.2017.02.016 · Cited by 576
“, 2010), NIX/BNIP3L (Novak et al., 2010; Zhang and Ney, 2008), BNIP3 (Zhang and Ney, 2009), FUNDC1 (Liu et al.”
BackgroundInfluentialPLEKHM1 Regulates Autophagosome-Lysosome Fusion through HOPS Complex and LC3/GABARAP Proteins
McEwan, D. G., Popovic, D., Gubas, A., Terawaki, S., Suzuki, H., Stadel, D., Coxon, F. P., Miranda de Stegmann, D., Bhogaraju, S., Maddi, K., et al. (2015) · Molecular Cell · doi:10.1016/j.molcel.2014.11.006 · Cited by 563
“, 2009a), Nix/BNiP3L (Novak et al., 2010), TBC1D5 (Popovic et al.”
BackgroundAtg8‐family interacting motif crucial for selective autophagy
Noda, N. N., Ohsumi, Y., & Inagaki, F. (2010) · FEBS Letters · doi:10.1016/j.febslet.2010.01.018 · Cited by 553
“Very recently, Nix has been shown to function as a mitophagy-specific receptor through the direct interaction with mammalian Atg8 homologues [13].”
BackgroundInfluentialThe Role of Autophagy in the Heart
Sciarretta, S., Maejima, Y., Zablocki, D., & Sadoshima, J. (2018) · Annual Review of Physiology · doi:10.1146/annurev-physiol-021317-121427 · Cited by 547
Atg8: an autophagy-related ubiquitin-like protein family.
Shpilka, T., Weidberg, H., Pietrokovski, S., & Elazar, Z. (2011) · Genome biology · doi:10.1186/gb-2011-12-7-226 · Cited by 543
mito-QC illuminates mitophagy and mitochondrial architecture in vivo
McWilliams, T. G., Prescott, A. R., Allen, G. F. G., Tamjar, J., Munson, M. J., Thomson, C., Muqit, M. M. K., & Ganley, I. G. (2016) · The Journal of Cell Biology · doi:10.1083/jcb.201603039 · Cited by 561
“Furthermore, our findings provoke a reassessment of how mitophagy is viewed as simply a protective response to mitotoxic damage or that it only occurs in specific physiological contexts such as reticulocyte development (Schweers et al., 2007; Mortensen et al., 2010; Novak et al., 2010).”
BackgroundA Diversity of Selective Autophagy Receptors Determines the Specificity of the Autophagy Pathway
Kirkin, V., & Rogov, V. V. (2019) · Molecular Cell · doi:10.1016/j.molcel.2019.09.005 · Cited by 536
Murrow, L. M., & Debnath, J. (2012) · Annual Review of Pathology Mechanisms of Disease · doi:10.1146/annurev-pathol-020712-163918 · Cited by 546
Laker, R. C., Drake, J. C., Wilson, R. J., Lira, V. A., Lewellen, B. M., Ryall, K. A., Fisher, C. C., Zhang, M., Saucerman, J. J., Goodyear, L. J., et al. (2017) · Nature Communications · doi:10.1038/s41467-017-00520-9 · Cited by 529
Interplay between ROS and autophagy in cancer cells, from tumor initiation to cancer therapy
Poillet-Perez, L., Despouy, G., Delage-Mourroux, R., & Boyer-Guittaut, M. (2015) · Redox Biology · doi:10.1016/j.redox.2014.12.003 · Cited by 503
Selective autophagy of intracellular organelles: Recent research advances
Li, W., He, P., Huang, Y., Li, Y.-F., Lu, J., Li, M., Kurihara, H., Luo, Z., Meng, T., Onishi, M., et al. (2020) · Theranostics · doi:10.7150/thno.49860 · Cited by 523
“NIX interacts with LC3 family proteins via its LIR motif to mediate autophagic clearance of mitochondria during reticulocyte maturation [45] (Figure 2).”
BackgroundAggrephagy: Selective Disposal of Protein Aggregates by Macroautophagy
Lamark, T., & Johansen, T. (2012) · International Journal of Cell Biology · doi:10.1155/2012/736905 · Cited by 514
“These are ATG32 and NIX/BNIP3L acting in mitophagy [130–132], NDP52 and optineurin in xenophagy [133, 134], and Stbd1 in degradation of glycogen [135].”
BackgroundZhu, Y., Maßen, S., Terenzio, M., Lang, V., Chen-Lindner, S., Eils, R., Novak, I., Đikić, I., Hamacher‐Brady, A., & Brady, N. R. (2012) · Journal of Biological Chemistry · doi:10.1074/jbc.m112.399345 · Cited by 504
“The mitochondrial uncoupler CCCP, which collapses the mitochondrial membrane potential, enhances Nix-driven mitophagy in a LIR-dependent manner (23).”
BackgroundMethodInfluentialKubli, D. A., Zhang, X., Lee, Y., Hanna, R. A., Quinsay, M. N., Nguyen, C. K., Jimenez, R., Petrosyan, S., Murphy, A. N., & Gustafsson, Å. B. (2013) · Journal of Biological Chemistry · doi:10.1074/jbc.m112.411363 · Cited by 476
“This is indicative of LC3II directly binding to mitochondrial autophagy receptors such as Bnip3 (25) and Nix (26, 27) in the remote zone.”
BackgroundMitophagy is triggered by mild oxidative stress in a mitochondrial fission dependent manner
Frank, M., Duvezin-Caubet, S., Koob, S., Occhipinti, A., Jagasia, R., Petcherski, A., Ruonala, M. O., Priault, M., Salin, B., & Reichert, A. S. (2012) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2012.08.007 · Cited by 468
“NIX, a BH3 domain containing protein [20,21] was reported to act as a mitochondrial receptor required for mitochondrial clearance in reticulocytes [22].”
BackgroundBiogenesis and Cargo Selectivity of Autophagosomes
Weidberg, H., Shvets, E., & Elazar, Z. (2011) · Annual Review of Biochemistry · doi:10.1146/annurev-biochem-052709-094552 · Cited by 466
Mitophagy in degenerative joint diseases
Sun, K., Jing, X., Guo, J., Yao, X., & Guo, F. (2020) · Autophagy · doi:10.1080/15548627.2020.1822097 · Cited by 471
Mitochondrial biogenesis and clearance: a balancing act
Ploumi, C., Daskalaki, I., & Tavernarakis, N. (2016) · FEBS Journal · doi:10.1111/febs.13820 · Cited by 479
Mitochondrial Function, Biology, and Role in Disease
Murphy, E., Ardehali, H., Balaban, R. S., Lisa, F. D., Dorn, G. W., Kitsis, R. N., Otsu, K., Ping, P., Rizzuto, R., Sack, M. N., et al. (2016) · Circulation Research · doi:10.1161/res.0000000000000104 · Cited by 476
Mitochondria and cell signalling
Tait, S. W. G., & Green, D. R. (2012) · Journal of Cell Science · doi:10.1242/jcs.099234 · Cited by 453
“Autophagosome elongation requires conjugation of LC3 (Atg8 in yeast) to the lipid phosphatidylethanolamine (PtdEtn).”
BackgroundInfluentialA Molecular Approach to Mitophagy and Mitochondrial Dynamics.
Yoo, S., & Jung, Y. (2018) · PubMed · doi:10.14348/molcells.2018.2277 · Cited by 457
“NIX/BNIP3L, BNIP3 and FUNDC1 Nip3-like protein X (NIX) and BCL2/Adenovirus E1B 19 kDa Interacting Protein 3 (BNIP3) contain a BH3 domain and interact with LC3 (Hanna et al., 2012; Novak et al., 2010).”
BackgroundYao, R.-Q., Ren, C., Xia, Z.-F., & Yao, Y.-M. (2021) · Autophagy · doi:10.1080/15548627.2020.1725377 · Cited by 441
“Mitophagy Outer mitochondrial membrane VDAC Mediating degradation of mitochondria in PINK1- and PRKN-dependent signaling pathway [29,30] RHOT1 MFN1/2 BNIP3L Mediating ubiquitin-independent degradation of mitochondria by directly interacting with MAP1LC3B [40,45,49] FUNDC1 [39,44,46] BNIP3 [41] AMBRA1 [50,51] BCL2LI3 […”
Mitochondrial quality control and muscle mass maintenance.
Romanello, V., & Sandri, M. (2016) · Frontiers in Physiology · doi:10.3389/fphys.2015.00422 · Cited by 434
“Subsequently, the autophagic adaptors optineurin, NDP52 (Lazarou et al., 2015) bind the phosphorylated ubiquitins tagging the OMM proteins with LC3 to initiate mitophagy.”
BackgroundInfluentialAutophagy promotes primary ciliogenesis by removing OFD1 from centriolar satellites
Tang, Z., Lin, M. G., Stowe, T. R., Chen, S., Zhu, M., Stearns, T., Franco, B., & Zhong, Q. (2013) · Nature · doi:10.1038/nature12606 · Cited by 414
Filimonenko, M., Isakson, P., Finley, K. D., Anderson, M. R., Jeong, H., Melia, T. J., Bartlett, B. J., Myers, K. M., Birkeland, H. C. G., Lamark, T., et al. (2010) · Molecular Cell · doi:10.1016/j.molcel.2010.04.007 · Cited by 449
“Termed ‘‘autophagy receptors,’’ they are involved in degradation of ubiquitinated bacteria (NDP52) (Thurston et al., 2009), mitochondria (NIX) (Novak et al., 2010; Sandoval et al., 2008), and protein aggregates (p62 and NBR1) (Kirkin et al., 2009; Pankiv et al., 2007).”
Ribosomopathies: There’s strength in numbers
Mills, E. W., & Green, R. (2017) · Science · doi:10.1126/science.aan2755 · Cited by 444
Mitochondrial homeostasis: The interplay between mitophagy and mitochondrial biogenesis
Palikaras, K., & Tavernarakis, N. (2014) · Experimental Gerontology · doi:10.1016/j.exger.2014.01.021 · Cited by 447
“BNIP3 and BNIP3L/NIX contain a cytoplasmic WXXL-like motif, which interacts with LC3 (the mammalian homolog of the yeast Atg8) and theGABA receptor-associated protein (GABARAP) in vivo and in vitro (Hanna et al., 2012; Novak et al., 2010; Schwarten et al., 2009).”
BackgroundMechanisms of Selective Autophagy
Lamark, T., & Johansen, T. (2021) · Annual Review of Cell and Developmental Biology · doi:10.1146/annurev-cellbio-120219-035530 · Cited by 429
Crosstalk Between Mammalian Autophagy and the Ubiquitin-Proteasome System
Kocatürk, N. M., & Gözüaçık, D. (2018) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2018.00128 · Cited by 442
“Through its LIR domain, NIX interacted with LC3, enabling engulfment of mitochondria by autophagosomes in reticulocytes (Novak et al., 2010).”
BackgroundReceptor-mediated mitophagy in yeast and mammalian systems
Liu, L., Sakakibara, K., Chen, Q., & Okamoto, K. (2014) · Cell Research · doi:10.1038/cr.2014.75 · Cited by 421
FKBP8 recruits LC3A to mediate Parkin‐independent mitophagy
Bhujabal, Z., Birgisdottir, Å. B., Sjøttem, E., Brenne, H. B., Øvervatn, A., Habisov, S., Kirkin, V., Lamark, T., & Johansen, T. (2017) · EMBO Reports · doi:10.15252/embr.201643147 · Cited by 428
“The known mitophagy receptors preferentially recruit a distinct ATG8 protein for mitophagy induction, NIX recruits GABARAP-L1 [17], while Bcl-2-L13, BNIP3, and FUNDC1 preferentially recruit LC3B [14 – 16].”
Regulation and Function of Autophagy during Cell Survival and Cell DeathPreprint
Das, G., Shravage, B. V., & Baehrecke, E. H. (2012) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a008813 · Cited by 420
“In animals, Parkin and Nix mediate the selective recruitment of mitochondria to autophagosomes (Narendra et al. 2008; Novak et al. 2010).”
BackgroundMitochondria removal by autophagy
Wang, K., & Klionsky, D. J. (2011) · Autophagy · doi:10.4161/auto.7.3.14502 · Cited by 380
“”(31) Nix is a mitochondrial outer membrane protein with the ability to bind to LC3/ GABARAP.(32,33) While Nix was initially reported to function in the maturation of reticulocytes,(34,35) it was recently shown to be important also for CCCP-induced mitophagy of depolarized mitochondria.”
BackgroundRoles of Autophagy in Oxidative Stress
Yun, H. R., Jo, Y. H., Kim, J., Shin, Y., Kim, S. S., & Choi, T. G. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21093289 · Cited by 413
“It directly recognizes autophagosome-sited GABARAP, and subsequently induces mitophagy [114,161].”
BackgroundDiverse Cellular Roles of Autophagy
Morishita, H., & Mizushima, N. (2019) · Annual Review of Cell and Developmental Biology · doi:10.1146/annurev-cellbio-100818-125300 · Cited by 376
Metadata
- Authors
- Novak, I., Kirkin, V., McEwan, D. G., Zhang, J., Wild, P., Rozenknop, A., Rogov, V., Löhr, F., Popovic, D., Occhipinti, A., Reichert, A. S., Terzic, J., Dötsch, V., Ney, P. A., & Dikic, I.
- Affiliations
- Mediterranean Institute for Life Sciences (HR)
- Goethe University Frankfurt (DE)
- St. Jude Children's Research Hospital (US)
- ORCID
- Venue
- The EMBO Reports
- Published
- 2009-12-11
- Volume
- 11
- Issue
- 1
- Pages
- 45-51
- ISSN
- 1469-221X (ISSN-L)
- 1469-3178
- PMC
- PMC2816619
- OpenAlex
- W2127440157
- Cited by
- 1,309
- References
- 35
- Citations by year
- 2026: 63 · 2025: 77 · 2024: 79 · 2023: 72 · 2022: 81 · 2021: 106 · 2020: 96 · 2019: 86 · 2018: 77 · 2017: 74 · 2016: 85 · 2015: 72 · 2014: 77 · 2013: 63 · 2012: 90
- FWCI
- 44.76
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- EMBO Reports (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Deutsche Forschungsgemeinschaft ((EXC 115).)
- Terry Fox Foundation
- National Institutes of Health (CA21765))
- National Cancer Institute (P 30CA 21765, P30CA021765)
- National Institute of Diabetes and Digestive and Kidney Diseases (DK074519, R21DK074519)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Autophagy in Disease and Therapy
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ubiquitin and proteasome pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Physiology › Calcium signaling and nucleotide metabolism
- Keywords
- Nix, selective autophagy, mitophagy, autophagy receptors, LC3, GABARAP, LC3-interacting region, mitochondrial clearance, mitochondrial damage, reticulocytes, erythroid differentiation, ubiquitin-like proteins
- MeSH terms
- Autophagy-Related Protein 8 Family, Amino Acid Sequence, Animals, Autophagy, Binding Sites, Cells, Cultured, Chlorocebus aethiops, Humans, Membrane Proteins, Microtubule-Associated Proteins, Mitochondria, Molecular Sequence Data, Protein Binding, Proto-Oncogene Proteins, Receptors, GABA-A, Reticulocytes, Substrate Specificity, Blotting, Western, COS Cells, Amino Acid Motifs, Mitochondrial Proteins, Tumor Suppressor Proteins, Saccharomyces cerevisiae Proteins, Ubiquitin-Protein Ligases, Mice
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