USP30 protects against oxygen-glucose deprivation/reperfusion induced mitochondrial fragmentation and ubiquitination and degradation of MFN2

被引：20

作者：

Chen, Chunli ^{[1
]}

Qin, Haiyun ^{[1
]}

Tang, Jiayu ^{[2
]}

Hu, Zhiping ^{[1
]}

Tan, Jieqiong ^{[3
,4
,5
]}

Zeng, Liuwang ^{[1
]}

机构：

[1] Cent South Univ, Xiangya Hosp 2, Dept Neurol, Changsha 410011, Hunan, Peoples R China

[2] Hunan Prov, Dept Neurol, Peoples Hosp 2, Changsha 410007, Hunan, Peoples R China

[3] Cent South Univ, Ctr Med Genet, Sch Life Sci, Changsha 410078, Hunan, Peoples R China

[4] Cent South Univ, Hunan Key Lab Med Genet, Changsha 410078, Hunan, Peoples R China

[5] Cent South Univ, Hunan Key Lab Anim Model Human Dis, Changsha 410078, Hunan, Peoples R China

来源：

AGING-US | 2021年 / 13卷 / 04期

基金：

中国国家自然科学基金;

关键词：

USP30; MFN2; mitochondria; oxygen-glucose deprivation/reperfusion (OGDR); ubiquitination; ISCHEMIC-STROKE; PROTEASOME; MORPHOLOGY; DISEASE;

D O I：

10.18632/aging.202629

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Cerebral ischemia-reperfusion induces mitochondrial fragmentation and dysfunction, which plays a critical role in the subsequent neuronal death and neurological impairment. Protection of mitochondria is an effective strategy to prevent neuronal damage after cerebral ischemia-reperfusion injury. USP30 is a deubiquitinating enzyme that localizes to the outer mitochondrial membrane. USP30 participates in the regulation of mitophagy and maintenance of mitochondrial morphology. In this study, the neuroprotective effect of USP30 and the underlying mechanisms were assessed in an ischemia-reperfusion injury model. SK-N-BE (2) cells were subjected to oxygen-glucose deprivation/reperfusion (OGDR) insult. Ubiquitination of mitochondrial proteins is increased during the early stage of reperfusion after oxygen-glucose deprivation (OGD), but the ubiquitination of cytoplasmic proteins exhibits no obvious changes. OGDR insult also induces rapid ubiquitination and degradation of the mitochondrial fusion protein mitofusin 2 (MFN2) in the early stage of reperfusion after OGD. Overexpression of MFN2 attenuates OGDR induced mitochondrial fragmentation. USP30 overexpression suppresses OGDR-induced ubiquitination and degradation of MFN2, and protects against mitochondrial fragmentation. Therefore, precisely targeting USP30 may provide a novel therapeutic strategy for cerebral ischemia-reperfusion related disorders.

引用

页码：6194 / 6204

页数：11

共 36 条

[11] E2-25K SUMOylation inhibits proteasome for cell death during cerebral ischemia/reperfusion [J].

Jeong, Eun Il ;

Chung, Hae Won ;

Lee, Won Jea ;

Kim, Seo-Hyun ;

Kim, Hyunjoo ;

Choi, Seon-Guk ;

Jung, Yong-Keun .

CELL DEATH & DISEASE, 2016, 7 :e2573-e2573

[12] Global brain ischemia in rats is associated with mitochondrial release and downregulation of Mfn2 in the cerebral cortex, but not the hippocampus [J].

Klacanova, Katarina ;

Kovalska, Maria ;

Chomova, Maria ;

Pilchova, Ivana ;

Tatarkova, Zuzana ;

Kaplan, Peter ;

Racay, Peter .

INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE, 2019, 43 (06) :2420-2428

[13] Hyperglycemia Alters Mitochondrial Fission and Fusion Proteins in Mice Subjected to Cerebral Ischemia and Reperfusion [J].

Kumari, Santosh ;

Anderson, Lavita ;

Farmer, Stephanie ;

Mehta, Suresh L. ;

Li, P. Andy .

TRANSLATIONAL STROKE RESEARCH, 2012, 3 (02) :296-304

[14] The Ubiquitin E3 Ligase TRAF6 Exacerbates Ischemic Stroke by Ubiquitinating and Activating Rac1 [J].

Li, Tao ;

Qin, Juan-Juan ;

Yang, Xia ;

Ji, Yan-Xiao ;

Guo, Fangliang ;

Cheng, Wen-Lin ;

Wu, Xiaolin ;

Gong, Fu-Han ;

Hong, Ying ;

Zhu, Xue-Yong ;

Gong, Jun ;

Wang, Zhihua ;

Huang, Zan ;

She, Zhi-Gang ;

Li, Hongliang .

JOURNAL OF NEUROSCIENCE, 2017, 37 (50) :12123-12140

[15] USP30 deubiquitylates mitochondrial Parkin substrates and restricts apoptotic cell death [J].

Liang, Jin-Rui ;

Martinez, Aitor ;

Lane, Jon D. ;

Mayor, Ugo ;

Clague, Michael J. ;

Urbe, Sylvie .

EMBO REPORTS, 2015, 16 (05) :618-627

[16] Mitochondria in Ischemic Stroke: New Insight and Implications [J].

Liu, Fan ;

Lu, Jianfei ;

Manaenko, Anatol ;

Tang, Junjia ;

Hu, Qin .

AGING AND DISEASE, 2018, 9 (05) :924-937

[17] Thrombolysis Guided by Perfusion Imaging up to 9 Hours after Onset of Stroke [J].

Ma, H. ;

Campbell, B. C. V. ;

Parsons, M. W. ;

Churilov, L. ;

Levi, C. R. ;

Hsu, C. ;

Kleinig, T. J. ;

Wijeratne, T. ;

Curtze, S. ;

Dewey, H. M. ;

Miteff, F. ;

Tsai, C. -H. ;

Lee, J. -T. ;

Phan, T. G. ;

Mahant, N. ;

Sun, M. -C. ;

Krause, M. ;

Sturm, J. ;

Grimley, R. ;

Chen, C. -H. ;

Hu, C. -J. ;

Wong, A. A. ;

Field, D. ;

Sun, Y. ;

Barber, P. A. ;

Sabet, A. ;

Jannes, J. ;

Jeng, J. -S. ;

Clissold, B. ;

Markus, R. ;

Lin, C. -H. ;

Lien, L. -M. ;

Bladin, C. F. ;

Christensen, S. ;

Yassi, N. ;

Sharma, G. ;

Bivard, A. ;

Desmond, P. M. ;

Yan, B. ;

Mitchell, P. J. ;

Thijs, V. ;

Carey, L. ;

Meretoja, A. ;

Davis, S. M. ;

Donnan, G. A. .

NEW ENGLAND JOURNAL OF MEDICINE, 2019, 380 (19) :1795-1803

[18] Mfn2 ubiquitination by PINK1/parkin gates the p97-dependent release of ER from mitochondria to drive mitophagy [J].

McLelland, Gian-Luca ;

Goiran, Thomas ;

Yi, Wei ;

Dorval, Genevieve ;

Chen, Carol X. ;

Lauinger, Nadine D. ;

Krahn, Andrea I. ;

Valimehr, Sepideh ;

Rakovic, Aleksander ;

Rouiller, Isabelle ;

Durcan, Thomas M. ;

Trempe, Jean-Francois ;

Fon, Edward A. .

ELIFE, 2018, 7

[19] Regulation of mitochondrial morphology by USP30, a deubiquitinating enzyme present in the mitochondrial outer membrane [J].

Nakamura, Nobuhiro ;

Hirose, Shigehisa .

MOLECULAR BIOLOGY OF THE CELL, 2008, 19 (05) :1903-1911

[20] Thrombectomy 6 to 24 Hours after Stroke with a Mismatch between Deficit and Infarct [J].

Nogueira, R. G. ;

Jadhav, A. P. ;

Haussen, D. C. ;

Bonafe, A. ;

Budzik, R. F. ;

Bhuva, P. ;

Yavagal, D. R. ;

Ribo, M. ;

Cognard, C. ;

Hanel, R. A. ;

Sila, C. A. ;

Hassan, A. E. ;

Millan, M. ;

Levy, E. I. ;

Mitchell, P. ;

Chen, M. ;

English, J. D. ;

Shah, Q. A. ;

Silver, F. L. ;

Pereira, V. M. ;

Mehta, B. P. ;

Baxter, B. W. ;

Abraham, M. G. ;

Cardona, P. ;

Veznedaroglu, E. ;

Hellinger, F. R. ;

Feng, L. ;

Kirmani, J. F. ;

Lopes, D. K. ;

Jankowitz, B. T. ;

Frankel, M. R. ;

Costalat, V. ;

Vora, N. A. ;

Yoo, A. J. ;

Malik, A. M. ;

Furlan, A. J. ;

Rubiera, M. ;

Aghaebrahim, A. ;

Olivot, J. -M. ;

Tekle, W. G. ;

Shields, R. ;

Graves, T. ;

Lewis, R. J. ;

Smith, W. S. ;

Liebeskind, D. S. ;

Saver, J. L. ;

Jovin, T. G. .

NEW ENGLAND JOURNAL OF MEDICINE, 2018, 378 (01) :11-21

← 1 2 3 4 →