Inhibition of mitoNEET induces Pink1-Parkin-mediated mitophagy
2
조회
0
다운로드
0
인용
0
참고문헌
키워드
초록
MitoNEET, a mitochondrial outer membrane protein containingthe Asn-Glu-Glu-Thr (NEET) sequence, controls the formation ofintermitochondrial junctions and confers autophagy resistance. Moreover, mitoNEET as a mitochondrial substrate undergoes ubiquitinationby activated Parkin during the initiation of mitophagy. Therefore, mitoNEET is linked to the regulation of autophagy andmitophagy. Mitophagy is the selective removal of the damagedor unnecessary mitochondria, which is crucial to sustaining mitochondrialquality control. In numerous human diseases, the accumulationof damaged mitochondria by impaired mitophagyhas been observed. However, the therapeutic strategy targetingof mitoNEET as a mitophagy-enhancing mediator requires furtherresearch. Herein, we confirmed that mitophagy is indeed activatedby mitoNEET inhibition. CCCP (carbonyl cyanide m-chlorophenylhydrazone), which leads to mitochondrial depolarization, inducesmitochondrial dysfunction and superoxide production. This, inturn, contributes to the induction of mitophagy; mitoNEET proteinlevels were initially increased before an increase in LC3-Ⅱ proteinfollowing CCCP treatment. Pharmacological inhibition ofmitoNEET using mitoNEET Ligand-1 (NL-1) promoted accumulationof Pink1 and Parkin, which are mitophagy-associated proteins,and activation of mitochondria–lysosome crosstalk, in comparisonto CCCP alone. Inhibition of mitoNEET using NL-1, or mitoNEETshRNA transfected into RAW264.7 cells, abrogated CCCP-inducedROS and mitochondrial cell death; additionally, it activated theexpression of PGC-1α and SOD2, regulators of oxidative metabolism. In particular, the increase in PGC-1α, which is a majorregulator of mitochondrial biogenesis, promotes mitochondrialquality control. These results indicated that mitoNEET is a potentialtherapeutic target in numerous human diseases to enhancemitophagy and protect cells by maintaining a network of healthymitochondria.
Abstract
MitoNEET, a mitochondrial outer membrane protein containingthe Asn-Glu-Glu-Thr (NEET) sequence, controls the formation ofintermitochondrial junctions and confers autophagy resistance. Moreover, mitoNEET as a mitochondrial substrate undergoes ubiquitinationby activated Parkin during the initiation of mitophagy. Therefore, mitoNEET is linked to the regulation of autophagy andmitophagy. Mitophagy is the selective removal of the damagedor unnecessary mitochondria, which is crucial to sustaining mitochondrialquality control. In numerous human diseases, the accumulationof damaged mitochondria by impaired mitophagyhas been observed. However, the therapeutic strategy targetingof mitoNEET as a mitophagy-enhancing mediator requires furtherresearch. Herein, we confirmed that mitophagy is indeed activatedby mitoNEET inhibition. CCCP (carbonyl cyanide m-chlorophenylhydrazone), which leads to mitochondrial depolarization, inducesmitochondrial dysfunction and superoxide production. This, inturn, contributes to the induction of mitophagy; mitoNEET proteinlevels were initially increased before an increase in LC3-Ⅱ proteinfollowing CCCP treatment. Pharmacological inhibition ofmitoNEET using mitoNEET Ligand-1 (NL-1) promoted accumulationof Pink1 and Parkin, which are mitophagy-associated proteins,and activation of mitochondria–lysosome crosstalk, in comparisonto CCCP alone. Inhibition of mitoNEET using NL-1, or mitoNEETshRNA transfected into RAW264.7 cells, abrogated CCCP-inducedROS and mitochondrial cell death; additionally, it activated theexpression of PGC-1α and SOD2, regulators of oxidative metabolism. In particular, the increase in PGC-1α, which is a majorregulator of mitochondrial biogenesis, promotes mitochondrialquality control. These results indicated that mitoNEET is a potentialtherapeutic target in numerous human diseases to enhancemitophagy and protect cells by maintaining a network of healthymitochondria.
참고문헌 (27)
- AshrafiG, "The pathways of mitophagy for quality control and clearance of mitochondria", Cell Death Differ, 20, pp.31~42 (2013)
- Tilokani L, "Mitochondrial dynamics : overview of molecular mechanisms", Essays Biochem, 62, pp.341~360 (2018)
- 엄지현, "Emerging role of mitophagy in human diseases and physiology", BMB Reports, 50(6), pp.299~307 (2017), 생화학분자생물학회
- Doblado L, "Mitophagy in human diseases", Int J Mol Sci, 22, pp.3903~ (2021)
- Lou G, "Mitophagy and neuroprotection", Trends Mol Med, 26, pp.8~20 (2020)
- Gkikas I, "The role of mitophagy in innate immunity", Front Immunol, 9, pp.1283~ (2018)
- Hung CM, "AMPK", ULK1 mediated phosphorylation of Parkin ACT domain mediates an early step in mitophagy, 2021, pp.7, eabg4544~
- Ga Hyun Park, "Precise control of mitophagy through ubiquitin proteasome system and deubiquitin proteases and their dysfunction in Parkinson’s disease", BMB Reports, 54(12), pp.592~600 (2021), 생화학분자생물학회
- 신우현, "The central regulator p62 between ubiquitin proteasome system and autophagy and its role in the mitophagy and Parkinson’s disease", BMB Reports, 53(1), pp.56~63 (2020), 생화학분자생물학회[DOI]
- Vernay A, "MitoNEETdependent formation of intermitochondrial junctions", Proc Natl Acad Sci U S A, 114, pp.8277~8282 (2017)
- Molino D, "Chemical targeting of NEET proteins reveals their function in mitochondrial morphodynamics", EMBO Rep, 21, pp.e49019~ (2020)
- Sohn YS, "NAF-1 and mitoNEET are central to human breast cancer proliferation by maintaining mitochondrial homeostasis and promoting tumor growth", Proc Natl Acad Sci U S A, 110, pp.14676~14681 (2013)
- Salem AF, "Mitochondrial biogenesis in epithelial cancer cells promotes breast cancer tumor growth and confers autophagy resistance", Cell Cycle, 11, pp.4174~4180 (2012)
- Tamir S, "Structure–function analysis of NEET proteins uncovers their role as key regulators of iron and ROS homeostasis in health and disease", Biochim Biophys Acta, 1853, pp.1294~1315 (2015)
- Yamano K, "The ubiquitin signal and autophagy : an orchestrated dance leading to mitochondrial degradation", EMBO Rep, 17, pp.300~316 (2016)
- Lazarou M, "PINK1 drives Parkin self-association and HECT-like E3 activity upstream of mitochondrial binding", J Cell Biol, 200, pp.163~172 (2013)
- Seabright AP, "AMPK activation induces mitophagy and promotes mitochondrial fission while activating TBK1 in a PINK1-Parkin independent manner", FASEB J, 34, pp.6284~6301 (2020)
- Herzig S, "AMPK : guardian of metabolism and mitochondrial homeostasis", Nat Rev Mol Cell Biol, 19, pp.121~135 (2018)
- Colca JR, "Identification of a novel mitochondrial protein("mitoNEET")cross-linked specifically by a thiazolidinedione photoprobe", Am J Physiol Endocrinol Metab, 286, pp.E252~ (2004)
- Park JS, "p62 prevents carbonyl cyanide m-chlorophenyl hydrazine(CCCP)-induced apoptotic cell death by activating Nrf2", Biochem Biophys Res Commun, 464, pp.1139~1144 (2015)
- Livingston MJ, "Clearance of damaged mitochondria via mitophagy is important to the protective effect of ischemic preconditioning in kidneys", Autophagy, 15, pp.2142~2162 (2019)
- Palikaras K, "Balancing mitochondrial biogenesis and mitophagy to maintain energy metabolism homeostasis", Cell Death Differ, 22, pp.1399~1401 (2015)
- Soohyun Lee, "Mitochondrial dysfunction induced by callyspongiolide promotes autophagy-dependent cell death", BMB Reports, 54(4), pp.227~232 (2021), 생화학분자생물학회
- Bakula D, "MitophAging : mitophagy in aging and disease", Front Cell Dev Biol, 8, pp.239~ (2020)
- Wang Bei, "AMPKα2 protects against the development of heart failure by enhancing mitophagy via PINK1 phosphorylation", Circ Res, 122, pp.712~729 (2019)
- Kusminski CM, "MitoNEETParkin effects in pancreatic α-and β-cells, cellular survival, and intrainsular cross talk", Diabetes, 65, pp.1534~1555 (2016)
- Lee S, "Inhibition of mitoNEET attenuates LPS-induced inflammation and oxidative stress", Cell Death Dis, 13, pp.127~ (2022)