التفاصيل البيبلوغرافية
| العنوان: |
A20 binding and inhibitor of nuclear factor kappa B (NF-jB)-1 (ABIN-1): a novel modulator of mitochondrial autophagy. |
| المؤلفون: |
Merline, Rosetta, Rödig, Heiko, Zeng-Brouwers, Jinyang, Poluzzi, Chiara, Tascher, Georg, Michaelis, Jonas, Lopez-Mosqueda, Jaime, Rhiner, Andrew, Huber, Lisa Sophie, Diehl, Valentina, Dikic, Ivan, Köge, Donat, Münch, Christian, Wygrecka, Malgorzata, Schaefer, Liliana |
| المصدر: |
American Journal of Physiology: Cell Physiology; Feb2023, Vol. 324 Issue 2, pC339-C352, 14p |
| مصطلحات موضوعية: |
NF-kappa B, MITOCHONDRIAL membranes, CELL death, HOMEOSTASIS, AUTOPHAGY, MITOCHONDRIA, MEMBRANE proteins, LYSOSOMES, MICROTUBULE-associated proteins |
| مستخلص: |
A20 binding inhibitor of nuclear factor kappa B (NF-κB)-1 (ABIN-1), a polyubiquitin-binding protein, is a signal-induced autophagy receptor that attenuates NF-κB-mediated inflammation and cell death. The present study aimed to elucidate the potential role of ABIN-1 in mitophagy, a biological process whose outcome is decisive in diverse physiological and pathological settings. Microtubule-associated proteins 1A/1B light chain 3B-II (LC3B-II) was found to be in complex with ectopically expressed hemagglutinin (HA)-tagged-full length (FL)-ABIN-1. Bacterial expression of ABIN-1 and LC3A and LC3B showed direct binding of ABIN-1 to LC3 proteins, whereas mutations in the LC3-interacting region (LIR) 1 and 2 motifs of ABIN-1 abrogated ABIN-1/LC3B-II complex formation. Importantly, induction of autophagy in HeLa cells resulted in colocalization of ABIN-1 with LC3B-II in autophagosomes and with lysosomal-associated membrane protein 1 (LAMP-1) in autophagolysosomes, leading to degradation of ABIN-1 with p62. Interestingly, ABIN-1 was found to translocate to damaged mitochondria in HeLa-mCherry-Parkin transfected cells. In line with this observation, clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9)-mediated deletion of ABIN-1 significantly inhibited the degradation of the mitochondrial outer membrane proteins voltage-dependent anion-selective channel 1 (VDAC-1), mitofusin-2 (MFN2), and translocase of outer mitochondrial membrane (TOM)20. In addition, short interfering RNA (siRNA)-mediated knockdown of ABIN-1 significantly decreased lysosomal uptake of mitochondria in HeLa cells expressing mCherry-Parkin and the fluorescence reporter mt-mKEIMA. Collectively, our results identify ABIN-1 as a novel and selective mitochondrial autophagy regulator that promotes mitophagy, thereby adding a new player to the complex cellular machinery regulating mitochondrial homeostasis. [ABSTRACT FROM AUTHOR] |
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| قاعدة البيانات: |
Complementary Index |
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