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Cited by 488

The DOI matches its Crossref record; 13 of the 13 references it cites were found in a registry or an index.

Modulation of Serines 17 and 24 in the LC3-interacting Region of Bnip3 Determines Pro-survival Mitophagy versus Apoptosis

Open access
Zhu, Yanyan, Massen, Stefan, Terenzio, Marco, Lang, Verena, Chen-Lindner, Silu, Eils, Roland, Novak, Ivana, Dikic, Ivan, Hamacher-Brady, Anne, Brady, Nathan R.·2013·Journal of Biological Chemistry

Abstract

BH3-only proteins integrate apoptosis and autophagy pathways, yet regulation and functional consequences of pathway cross-talk are not fully resolved. The BH3-only protein Bnip3 is an autophagy receptor that signals autophagic degradation of mitochondria (mitophagy) via interaction of its LC3-interacting region (LIR) with Atg8 proteins. Here we report that phosphorylation of serine residues 17 and 24 flanking the Bnip3 LIR promotes binding to specific Atg8 members LC3B and GATE-16. Using quantitative multispectral image-based flow cytometry, we demonstrate that enhancing Bnip3-Atg8 interactions via phosphorylation-mimicked LIR mutations increased mitochondrial sequestration, lysosomal delivery, and degradation. Importantly, mitochondria were targeted by mitophagy prior to cytochrome c release, resulting in reduced cellular cytochrome c release capacity. Intriguingly, pro-survival Bcl-x L positively regulated Bnip3 binding to LC3B, sequestration, and mitochondrial autophagy, further supporting an anti-apoptotic role for Bnip3-induced mitophagy. The ensemble of these results demonstrates that the phosphorylation state of the Bnip3 LIR signals either the induction of apoptosis or pro-survival mitophagy. Background: Bnip3 is both a pro-apoptotic BH3-only protein and a mitochondrial autophagy receptor. Results: Serine phosphorylation of the Bnip3 LC3-interacting region (LIR) increased binding to Atg8 members and consequently mitophagy, in a manner positively regulated by Bcl-x L . Conclusion: The Bnip3 LIR activity state determines either pro-survival mitophagy or mitochondrial apoptosis. Significance: Bnip3-induced mitophagy is serine kinase-regulated and thus a targetable pathway.

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Metadata

Authors
Zhu, Y., Massen, S., Terenzio, M., Lang, V., Chen-Lindner, S., Eils, R., Novak, I., Dikic, I., Hamacher-Brady, A., & Brady, N. R.
Venue
Journal of Biological Chemistry
Publisher
Elsevier BV
Published
2013-01
Volume
288
Issue
2
Pages
1099-1113
ISSN
0021-9258 (ISSN-L)
OpenAlex
W2144450295
Cited by
488
References
13
FWCI
12.93
Type
journal article
Language
en
Open access
hybrid

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CoChat. (2026). Citation check: Modulation of Serines 17 and 24 in the LC3-interacting Region of Bnip3 Determines Pro-survival Mitophagy versus Apoptosis. https://app.cochat.ai/papers/10.1074/jbc.m112.399345
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Zhu, Y., Massen, S., Terenzio, M., Lang, V., Chen-Lindner, S., Eils, R., Novak, I., Dikic, I., Hamacher-Brady, A., & Brady, N. R. (2013). Modulation of Serines 17 and 24 in the LC3-interacting Region of Bnip3 Determines Pro-survival Mitophagy versus Apoptosis. Journal of Biological Chemistry. https://doi.org/10.1074/jbc.m112.399345

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