Electroacupuncture at GV20‑GB7 regulates mitophagy to protect against neurological deficits following intracerebral hemorrhage via inhibition of apoptosis

Guan,Ruiqiao; Li,Zhihao; Dai,Xiaohong; Zou,Wei; Yu,Xueping; Liu,Hao; Chen,Qiuxin; Teng,Wei; Liu,Peng; Liu,Xiaoying; Dong,Shanshan

doi:10.3892/mmr.2021.12131

Electroacupuncture at GV20‑GB7 regulates mitophagy to protect against neurological deficits following intracerebral hemorrhage via inhibition of apoptosis

Authors:
- Ruiqiao Guan
- Zhihao Li
- Xiaohong Dai
- Wei Zou
- Xueping Yu
- Hao Liu
- Qiuxin Chen
- Wei Teng
- Peng Liu
- Xiaoying Liu
- Shanshan Dong
View Affiliations

Affiliations: Department of Integrated Chinese and Western Medicine, Zhongshan Hospital, Fudan University, Shanghai 200032, P.R. China, Department of Acupuncture and Moxibustion, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Chinese Medicine, Shanghai 200437, P.R. China, Department of Clinical Medicine, Heilongjiang University of Chinese Medicine, Harbin, Heilongjiang 150040, P.R. China, Department of Acupuncture and Moxibustion, Tongde Hospital of Zhejiang Province, Hangzhou, Zhejiang 315099, P.R. China
Published online on: May 5, 2021 https://doi.org/10.3892/mmr.2021.12131
Article Number: 492
Copyright: © Guan et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

The acupuncture penetrating line of Baihui (GV20) to Qubin (GB7) spans the parietal, frontal and temporal lobes. The present study aimed to elucidate the mechanism by which electroacupuncture (EA) at GV20‑GB7 regulates mitophagy in intracerebral hemorrhage (ICH) and whether it serves a neuroprotective role. A whole blood‑induced ICH model was used. Mitophagy‑regulating proteins, including BCL/adenovirus E1B 19 kDa‑interacting protein 3 (BNIP3), PTEN‑induced putative kinase 1 (PINK1), Parkin and apoptosis‑associated proteins were detected by western blotting; autophagy following ICH was evaluated by immunofluorescent techniques; morphological characteristics of mitophagy were observed using transmission electron microscopy; and TUNEL assay was performed to determine the number of apoptotic cells. Immunohistochemistry was used to detect p53 expression. The protective role of EA (GV20‑GB7) via enhanced mitophagy and suppressed apoptosis in ICH was further confirmed by decreased modified neurological severity score. The results showed that EA (GV20‑GB7) treatment upregulated mitochondrial autophagy following ICH and inhibited apoptotic cell death. The mechanism underlying EA (GV20‑GB7) treatment may involve inhibition of p53, an overlapping protein of autophagy and apoptosis. EA (GV20‑GB7) treatment decreased neurobehavioral deficits following ICH but pretreatment with 3‑methyladenine counteracted the beneficial effects of EA (GV20‑GB7) treatment. In conclusion, EA (GV20‑GB7) improved recovery from ICH by regulating the balance between mitophagy and apoptosis.

View Figures

View References

1	Caplan LR: Intracerebral haemorrhage. Lancet. 339:656–658. 1992. View Article : Google Scholar : PubMed/NCBI
2	Broderick J, Connolly S, Feldmann E, Hanley D, Kase C, Krieger D, Mayberg M, Morgenstern L, Ogilvy CS, Vespa P, et al: Guidelines for the management of spontaneous intracerebral hemorrhage in adults: 2007 update: A guideline from the American Heart Association/American Stroke Association Stroke Council, High Blood Pressure Research Council, and the Quality of Care and Outcomes in Research Interdisciplinary Working Group. Stroke. 38:2001–2023. 2007. View Article : Google Scholar : PubMed/NCBI
3	Counsell C, Boonyakarnkul S, Dennis M, Sandercock P, Bamford J, Burn J and Warlow C: Primary intracerebral haemorrhage in the oxfordshire community stroke Project. Cerebrovascular Dis. 5:26–34. 1995. View Article : Google Scholar
4	Keep RF, Hua Y and Xi G: Intracerebral haemorrhage: Mechanisms of injury and therapeutic targets. Lancet Neurol. 11:720–731. 2012. View Article : Google Scholar : PubMed/NCBI
5	Nehls DG, Mendelow AD, Graham DI, Sinar EJ and Teasdale GM: Experimental intracerebral hemorrhage: Progression of hemodynamic changes after production of a spontaneous mass lesion. Neurosurgery. 23:439–444. 1988. View Article : Google Scholar : PubMed/NCBI
6	Belur PK, Chang JJ, He S, Emanuel BA and Mack WJ: Emerging experimental therapies for intracerebral hemorrhage: Targeting mechanisms of secondary brain injury. Neurosurg Focus. 34:E92013. View Article : Google Scholar : PubMed/NCBI
7	Levine B and Kroemer G: Autophagy in the pathogenesis of disease. Cell. 132:27–42. 2008. View Article : Google Scholar : PubMed/NCBI
8	Niu M, Dai X, Zou W, Yu X, Teng W, Chen Q, Sun X, Yu W, Ma H and Liu P: Autophagy, endoplasmic reticulum stress and the unfolded protein response in intracerebral hemorrhage. Transl Neurosci. 8:37–48. 2017. View Article : Google Scholar : PubMed/NCBI
9	Klionsky DJ and Emr SD: Autophagy as a regulated pathway of cellular degradation. Science. 290:1717–1721. 2000. View Article : Google Scholar : PubMed/NCBI
10	Wang K and Klionsky DJ: Mitochondria removal by autophagy. Autophagy. 7:297–300. 2014. View Article : Google Scholar
11	Goldman SJ, Taylor R, Zhang Y and Jin S: Autophagy and the degradation of mitochondria. Mitochondrion. 10:309–315. 2010. View Article : Google Scholar : PubMed/NCBI
12	Graef M and Nunnari J: A role for mitochondria in autophagy regulation. Autophagy. 7:1245–1246. 2011. View Article : Google Scholar : PubMed/NCBI
13	Wei H, Liu L and Chen Q: Selective removal of mitochondria via mitophagy: Distinct pathways for different mitochondrial stresses. Biochim Biophys Acta. 1853:2784–2790. 2015. View Article : Google Scholar : PubMed/NCBI
14	Lin C, Chao H, Li Z, Xu X, Liu Y, Hou L, Liu N and Ji J: Melatonin attenuates traumatic brain injury-induced inflammation: A possible role for mitophagy. J Pineal Res. 61:177–186. 2016. View Article : Google Scholar : PubMed/NCBI
15	Yuan Y, Zheng Y, Zhang X, Chen Y, Wu X, Wu J, Shen Z, Jiang L, Wang L, Yang W, et al: BNIP3L/NIX-mediated mitophagy protects against ischemic brain injury independent of PARK2. Autophagy. 13:1754–1766. 2017. View Article : Google Scholar : PubMed/NCBI
16	Li J, Lu J, Mi Y, Shi Z, Chen C, Riley J and Zhou C: Voltage-dependent anion channels (VDACs) promote mitophagy to protect neuron from death in an early brain injury following a subarachnoid hemorrhage in rats. Brain Res. 1573:74–83. 2014. View Article : Google Scholar : PubMed/NCBI
17	Yang Y, Xing D, Zhou F and Chen Q: Mitochondrial autophagy protects against heat shock-induced apoptosis through reducing cytosolic cytochrome c release and downstream caspase-3 activation. Biochem Biophys Res Commun. 395:190–195. 2010. View Article : Google Scholar : PubMed/NCBI
18	Colbert AP, Spaulding K, Larsen A, Ahn AC and Cutro JA: Electrodermal activity at acupoints: Literature review and recommendations for reporting clinical trials. J Acupunct and Meridian Stud. 4:5–13. 2011. View Article : Google Scholar : PubMed/NCBI
19	Zhang S, Wu B, Liu M, Li N, Zeng X, Liu H, Yang Q, Han Z, Rao P and Wang D; all Investigators, : Acupuncture efficacy on ischemic stroke recovery: Multicenter randomized controlled trial in China. Stroke. 46:1301–1306. 2015. View Article : Google Scholar : PubMed/NCBI
20	Langevin HM, Schnyer R, MacPherson H, Davis R, Harris RE, Napadow V, Wayne PM, Milley RJ, Lao L, Stener-Victorin E, et al: Manual and electrical needle stimulation in acupuncture research: Pitfalls and challenges of heterogeneity. J Altern Complement Med. 21:113–128. 2015. View Article : Google Scholar : PubMed/NCBI
21	Zhou F, Guo J, Cheng J, Wu G and Xia Y: Electroacupuncture increased cerebral blood flow and reduced ischemic brain injury: Dependence on stimulation intensity and frequency. J Appl Physiol (1985). 111:1877–1887. 2011. View Article : Google Scholar : PubMed/NCBI
22	Zhu Y, Deng L, Tang H, Gao X, Wang Y, Guo K, Kong J and Yang C: Electroacupuncture improves neurobehavioral function and brain injury in rat model of intracerebral hemorrhage. Brain Res Bull. 131:123–132. 2017. View Article : Google Scholar : PubMed/NCBI
23	Li HQ, Li Y, Chen ZX, Zhang XG, Zheng XW, Yang WT, Chen S and Zheng GQ: Electroacupuncture exerts neuroprotection through caveolin-1 mediated molecular pathway in intracerebral hemorrhage of rats. Neural Plast. 2016:73082612016. View Article : Google Scholar : PubMed/NCBI
24	Ting Z, Jianbin Z and Luqi H: Protective effect of electroacupuncture on neurons autophagy in perfusion period of cerebral ischemia. Neurosci Lett. 661:41–45. 2017. View Article : Google Scholar : PubMed/NCBI
25	Wu Z, Zou Z, Zou R, Zhou X and Cui S: Electroacupuncture pretreatment induces tolerance against cerebral ischemia/reperfusion injury through inhibition of the autophagy pathway. Mol Med Rep. 11:4438–4446. 2015. View Article : Google Scholar : PubMed/NCBI
26	Liu W, Shang G, Yang S, Huang J, Xue X, Lin Y, Zheng Y, Wang X, Wang L, Lin R, et al: Electroacupuncture protects against ischemic stroke by reducing autophagosome formation and inhibiting autophagy through the mTORC1-ULK1 complex-Beclin1 pathway. Int J Mol Med. 37:309–318. 2016. View Article : Google Scholar : PubMed/NCBI
27	Wu ZQ, Cui SY, Zhu L and Zou ZQ: Study on the mechanism of mTOR-Mediated autophagy during electroacupuncture pretreatment against cerebral ischemic injury. Evid Based Complement Alternat Med. 2016:91215972016. View Article : Google Scholar : PubMed/NCBI
28	Zou W, Chen QX, Sun XW, Chi QB, Kuang HY, Yu XP and Dai XH: Acupuncture inhibits Notch1 and Hes1 protein expression in the basal ganglia of rats with cerebral hemorrhage. Neural Regen Res. 10:457–462. 2015. View Article : Google Scholar : PubMed/NCBI
29	Liu H, Sun X, Zou W, Leng M, Zhang B, Kang X, He T and Wang H: Scalp acupuncture attenuates neurological deficits in a rat model of hemorrhagic stroke. Complement Ther Med. 32:85–90. 2017. View Article : Google Scholar : PubMed/NCBI
30	Health N: Guide for the care and use of laboratory animals. NIH contract No. No1-RR-2-2135. 11–28. 1985.
31	Guan R, Zou W, Dai X, Yu X, Liu H, Chen Q and Teng W: Mitophagy, a potential therapeutic target for stroke. J Biomed Sci. 25:872018. View Article : Google Scholar : PubMed/NCBI
32	Li Q, Zhang T, Wang J, Zhang Z, Zhai Y, Yang GY and Sun X: Rapamycin attenuates mitochondrial dysfunction via activation of mitophagy in experimental ischemic stroke. Biochem Biophys Res Commun. 444:182–188. 2014. View Article : Google Scholar : PubMed/NCBI
33	Di Y, He YL, Zhao T, Huang X, Wu KW, Liu SH, Zhao YQ, Fan M, Wu LY and Zhu LL: Methylene blue reduces acute cerebral ischemic injury via the induction of mitophagy. Mol Med. 21:420–429. 2015. View Article : Google Scholar : PubMed/NCBI
34	Jing CH, Wang L, Liu PP, Wu C, Ruan D and Chen G: Autophagy activation is associated with neuroprotection against apoptosis via a mitochondrial pathway in a rat model of subarachnoid hemorrhage. Neuroscience. 213:144–153. 2012. View Article : Google Scholar : PubMed/NCBI
35	Liu XY, Dai XH, Zou W, Yu XP, Teng W, Wang Y, Yu WW, Ma HH, Chen QX, Liu P, et al: Acupuncture through Baihui (DU20) to Qubin (GB7) mitigates neurological impairment after intracerebral hemorrhage. Neural Regen Res. 13:1425–1432. 2018. View Article : Google Scholar : PubMed/NCBI
36	Zhang B, Dai XH, Yu XP, Zou W, Teng W, Sun XW, Yu WW, Liu H, Wang H, Sun MJ and Li M: Baihui (DU20)-penetrating-Qubin (GB7) acupuncture inhibits apoptosis in the perihemorrhagic penumbra. Neural Regen Res. 13:1602–1608. 2018. View Article : Google Scholar : PubMed/NCBI
37	Wang C, Hu Q and Shen HM: Pharmacological inhibitors of autophagy as novel cancer therapeutic agents. Pharmacol Res. 105:164–175. 2016. View Article : Google Scholar : PubMed/NCBI
38	Hua XB: On animal acupoints. J Tradit Chi Med. 7:301–304. 1987.PubMed/NCBI
39	Jittiwat J: Laser Acupuncture at GV20 improves brain damage and oxidative stress in animal model of focal ischemic stroke. J Acupunct Meridian Stud. 10:324–330. 2017. View Article : Google Scholar : PubMed/NCBI
40	Yin CS, Jeong HS, Park HJ, Baik Y, Yoon MH, Choi CB and Koh HG: A proposed transpositional acupoint system in a mouse and rat model. Res Vet Sci. 84:159–165. 2008. View Article : Google Scholar : PubMed/NCBI
41	Han HJ, Park SJ, Soh KS, Myoung HS, Lee KJ, Ogay V and Lee YH: Electrical characterization of proposed transpositional acupoints on the urinary bladder meridian in a rat model. Evid Based Complement Alternat Med. 2011:2954752011. View Article : Google Scholar : PubMed/NCBI
42	Chen J, Sanberg PR, Li Y, Wang L, Lu M, Willing AE, Sanchez-Ramos J and Chopp M: Intravenous administration of human umbilical cord blood reduces behavioral deficits after stroke in rats. Stroke. 32:2682–2688. 2001. View Article : Google Scholar : PubMed/NCBI
43	Choe SC, Hamacher-Brady A and Brady NR: Autophagy capacity and sub-mitochondrial heterogeneity shape Bnip3-induced mitophagy regulation of apoptosis. Cell Commun Signal. 13:372015. View Article : Google Scholar : PubMed/NCBI
44	Gross A, McDonnell JM and Korsmeyer SJ: BCL-2 family members and the mitochondria in apoptosis. Genes Dev. 13:1899–1911. 1999. View Article : Google Scholar : PubMed/NCBI
45	Chen B, Wang G, Li W, Liu W, Lin R, Tao J, Jiang M, Chen L and Wang Y: Memantine attenuates cell apoptosis by suppressing the calpain-caspase-3 pathway in an experimental model of ischemic stroke. Exp Cell Res. 351:163–172. 2017. View Article : Google Scholar : PubMed/NCBI
46	Wagner DC, Riegelsberger UM, Michalk S, Hartig W, Kranz A and Boltze J: Cleaved caspase-3 expression after experimental stroke exhibits different phenotypes and is predominantly non-apoptotic. Brain Res. 1381:237–242. 2011. View Article : Google Scholar : PubMed/NCBI
47	Yan J, Yun H, Yang Y, Jing B, Feng C and Song-bin F: Upregulation of BNIP3 promotes apoptosis of lung cancer cells that were induced by p53. Biochem Biophys Res Commun. 346:501–507. 2006. View Article : Google Scholar : PubMed/NCBI
48	Tasdemir E, Chiara Maiuri M, Morselli E, Criollo A, D'Amelio M, Djavaheri-Mergny M, Cecconi F, Tavernarakis N and Kroemer G: A dual role of p53 in the control of autophagy. Autophagy. 4:810–814. 2008. View Article : Google Scholar : PubMed/NCBI
49	Sims NR and Muyderman H: Mitochondria, oxidative metabolism and cell death in stroke. Biochim Biophys Acta. 1802:80–91. 2010. View Article : Google Scholar : PubMed/NCBI
50	Kubli DA and Gustafsson AB: Mitochondria and mitophagy: The yin and yang of cell death control. Circ Res. 111:1208–1221. 2012. View Article : Google Scholar : PubMed/NCBI
51	Zhang X, Yan H, Yuan Y, Gao J, Shen Z, Cheng Y, Shen Y, Wang RR, Wang X, Hu WW, et al: Cerebral ischemia-reperfusion-induced autophagy protects against neuronal injury by mitochondrial clearance. Autophagy. 9:1321–1333. 2013. View Article : Google Scholar : PubMed/NCBI
52	Shen Z, Zheng Y, Wu J, Chen Y, Wu X, Zhou Y, Yuan Y, Lu S, Jiang L, Qin Z, et al: PARK2-dependent mitophagy induced by acidic postconditioning protects against focal cerebral ischemia and extends the reperfusion window. Autophagy. 13:473–485. 2017. View Article : Google Scholar : PubMed/NCBI
53	Baek SH, Noh AR, Kim KA, Akram M, Shin YJ, Kim ES, Yu SW, Majid A and Bae ON: Modulation of mitochondrial function and autophagy mediates carnosine neuroprotection against ischemic brain damage. Stroke. 45:2438–2443. 2014. View Article : Google Scholar : PubMed/NCBI
54	Shi RY, Zhu SH, Li V, Gibson SB, Xu XS and Kong JM: BNIP3 interacting with LC3 triggers excessive mitophagy in delayed neuronal death in stroke. CNS Neurosci Ther. 20:1045–1055. 2014. View Article : Google Scholar : PubMed/NCBI
55	Wu M, Lu G, Lao YZ, Zhang H, Zheng D, Zheng ZQ, Yi J, Xiang Q, Wang LM, Tan HS, et al: Garciesculenxanthone B induces PINK1-Parkin-mediated mitophagy and prevents ischemia-reperfusion brain injury in mice. Acta Pharmacol Sin. 42:199–208. 2021. View Article : Google Scholar : PubMed/NCBI
56	Yin ZL, Meng ZX, Ge S, Zhang MJ and Huang LH: Clinical observation of dynamic scalp acupuncture combined with task-oriented mirror therapy for upper limbs function impairment in patients with hemiplegia after ischemic stroke. Zhongguo Zhen Jiu. 40:918–922. 2020.(In Chinese). PubMed/NCBI
57	Wang WW, Xie CL, Lu L and Zheng GQ: A systematic review and meta-analysis of Baihui (GV20)-based scalp acupuncture in experimental ischemic stroke. Sci Rep. 4:39812014. View Article : Google Scholar : PubMed/NCBI
58	Zheng GQ, Zhao ZM, Wang Y, Gu Y, Li Y, Chen XM, Fu SP and Shen J: Meta-analysis of scalp acupuncture for acute hypertensive intracerebral hemorrhage. J Altern Complement Med. 17:293–299. 2011. View Article : Google Scholar : PubMed/NCBI
59	Lang Y, Cui FY, Li KS, Tan ZJ and Zou YH: Imaging observation of scalp acupuncture on brain gray matter injury in stroke patients with cerebral infarction. Zhongguo Zhong Xi Yi Jie He Za Zhi. 36:294–299. 2016.(In Chinese). PubMed/NCBI
60	Wang HQ, Bao CL, Jiao ZH and Dong GR: Efficacy and safety of penetration acupuncture on head for acute intracerebral hemorrhage: A randomized controlled study. Medicine (Baltimore). 95:e55622016. View Article : Google Scholar : PubMed/NCBI
61	Sun ST, Li SR, Zhu YZ, Chen SL, Wan GZ, Sun YZ, Hou GW and Yu ZH: Clinical study on 500 cases of cerebro-vascular hemiplegia treated by acupuncture through baihui to qubin. J Tradit Chin Med. 5:167–170. 1985.PubMed/NCBI
62	Wu Y, Wang X, Guo H, Zhang B, Zhang XB, Shi ZJ and Yu L: Synthesis and screening of 3-MA derivatives for autophagy inhibitors. Autophagy. 9:595–603. 2013. View Article : Google Scholar : PubMed/NCBI
63	Shao A, Wang Z, Wu H, Dong X, Li Y, Tu S, Tang J, Zhao M, Zhang J and Hong Y: Enhancement of autophagy by histone deacetylase inhibitor trichostatin a ameliorates neuronal apoptosis after subarachnoid hemorrhage in rats. Mol Neurobiol. 53:18–27. 2016. View Article : Google Scholar : PubMed/NCBI
64	Xia DY, Li W, Qian HR, Yao S, Liu JG and Qi XK: Ischemia preconditioning is neuroprotective in a rat cerebral ischemic injury model through autophagy activation and apoptosis inhibition. Braz J Med Biol Res. 46:580–588. 2013. View Article : Google Scholar : PubMed/NCBI
65	Ma H, Chen H, Dong A, Wang Y, Bian Y and Xie K: Hydrogen-rich saline attenuates hyperalgesia and reduces cytokines in rats with post-herpetic neuralgia via activating autophagy. Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi. 33:155–158. 2017.(In Chinese). PubMed/NCBI
66	Tang Y, Cai QH, Wang YJ, Fan SH, Zhang ZF, Xiao MQ, Zhu JY, Wu DM, Lu J and Zheng YL: Protective effect of autophagy on endoplasmic reticulum stress induced apoptosis of alveolar epithelial cells in rat models of COPD. Biosci Rep. 37:BSR201708032017. View Article : Google Scholar : PubMed/NCBI
67	Wu Q, Gao C, Wang H, Zhang X, Li Q, Gu Z, Shi X, Cui Y, Wang T, Chen X, et al: Mdivi-1 alleviates blood-brain barrier disruption and cell death in experimental traumatic brain injury by mitigating autophagy dysfunction and mitophagy activation. Int J Biochem Cell Biol. 94:44–55. 2018. View Article : Google Scholar : PubMed/NCBI
68	Guo Z, Cao G, Yang H, Zhou H, Li L, Cao Z, Yu B and Kou J: A combination of four active compounds alleviates cerebral ischemia-reperfusion injury in correlation with inhibition of autophagy and modulation of AMPK/mTOR and JNK pathways. J Neurosci Res. 92:1295–1306. 2014. View Article : Google Scholar : PubMed/NCBI
69	Chen X, Wang L, Deng Y, Li X, Li G, Zhou J, Cheng D, Yang Y, Yang Q, Chen G and Wang G: Inhibition of autophagy prolongs recipient survival through promoting CD8(+) T cell apoptosis in a rat liver transplantation model. Front Immunol. 10:13562019. View Article : Google Scholar : PubMed/NCBI
70	Cao S, Shrestha S, Li J, Yu X, Chen J, Yan F, Ying G, Gu C, Wang L and Chen G: Melatonin-mediated mitophagy protects against early brain injury after subarachnoid hemorrhage through inhibition of NLRP3 inflammasome activation. Sci Rep. 7:24172017. View Article : Google Scholar : PubMed/NCBI
71	Zuo W, Zhang S, Xia CY, Guo XF, He WB and Chen NH: Mitochondria autophagy is induced after hypoxic/ischemic stress in a Drp1 dependent manner: The role of inhibition of Drp1 in ischemic brain damage. Neuropharmacology. 86:103–115. 2014. View Article : Google Scholar : PubMed/NCBI
72	Hanna RA, Quinsay MN, Orogo AM, Giang K, Rikka S and Gustafsson AB: Microtubule-associated protein 1 light chain 3 (LC3) interacts with Bnip3 protein to selectively remove endoplasmic reticulum and mitochondria via autophagy. J Biol Chem. 287:19094–19104. 2012. View Article : Google Scholar : PubMed/NCBI
73	Zhang J and Ney PA: Role of BNIP3 and NIX in cell death, autophagy, and mitophagy. Cell Death Differ. 16:939–946. 2009. View Article : Google Scholar : PubMed/NCBI
74	Tan H, Wu Z, Wang H, Bai B, Li Y, Wang X, Zhai B, Beach TG and Peng J: Refined phosphopeptide enrichment by phosphate additive and the analysis of human brain phosphoproteome. Protemomics. 15:500–507. 2015. View Article : Google Scholar : PubMed/NCBI
75	Liu L, Sakakibara K, Chen Q and Okamoto K: Receptor-mediated mitophagy in yeast and mammalian systems. Cell Res. 24:787–795. 2014. View Article : Google Scholar : PubMed/NCBI
76	Kissová I, Plamondon L-T, Brisson L, Priault M, Renouf V, Schaeffer J, Camougrand N and Manon S: Evaluation of the roles of apoptosis, autophagy, and mitophagy in the loss of plating efficiency induced by Bax expression in yeast. J Biol Chem. 281:36187–36197. 2006. View Article : Google Scholar
77	Li XX, Tsoi B, Li YF, Kurihara H and He RR: Cardiolipin and its different properties in mitophagy and apoptosis. J Histochem Cytochem. 63:301–311. 2015. View Article : Google Scholar : PubMed/NCBI
78	Levine B, Sinha SC and Kroemer G: Bcl-2 family members: Dual regulators of apoptosis and autophagy. Autophagy. 4:600–606. 2008. View Article : Google Scholar
79	Ney PA: Mitochondrial autophagy: Origins, significance, and role of BNIP3 and NIX. Biochim Biophys Acta. 1853:2775–2783. 2015. View Article : Google Scholar : PubMed/NCBI
80	Feng X, Liu X, Zhang W and Xiao W: p53 directly suppresses BNIP3 expression to protect against hypoxia-induced cell death. EMBO J. 30:3397–3415. 2011. View Article : Google Scholar : PubMed/NCBI
81	Hoshino A, Matoba S, Iwai-Kanai E, Nakamura H, Kimata M, Nakaoka M, Katamura M, Okawa Y, Ariyoshi M, Mita Y, et al: p53-TIGAR axis attenuates mitophagy to exacerbate cardiac damage after ischemia. J Mol Cell Cardiol. 52:175–184. 2012. View Article : Google Scholar : PubMed/NCBI
82	Marino G, Niso-Santano M, Baehrecke EH and Kroemer G: Self-consumption: The interplay of autophagy and apoptosis. Nat Rev Mol Cell Biol. 15:81–94. 2014. View Article : Google Scholar : PubMed/NCBI
83	Jevtić G, Nikolić T, Mirčić A, Stojković T, Velimirović M, Trajković V, Marković I, Trbovich AM, Radonjić NV and Petronijević ND: Mitochondrial impairment, apoptosis and autophagy in a rat brain as immediate and long-term effects of perinatal phencyclidine treatment-influence of restraint stress. Prog Neuropsychopharmacol Biol Psychiatry. 66:87–96. 2016. View Article : Google Scholar
84	Chipuk JE, Kuwana T, Bouchier-Hayes L, Droin NM, Newmeyer DD, Schuler M and Green DR: Direct activation of Bax by p53 mediates mitochondrial membrane permeabilization and apoptosis. Science. 303:1010–1014. 2004. View Article : Google Scholar : PubMed/NCBI
85	Livesey KM, Kang R, Vernon P, Buchser W, Loughran P, Watkins SC, Zhang L, Manfredi JJ, Zeh HJ III, Li L, et al: p53/HMGB1 complexes regulate autophagy and apoptosis. Cancer Res. 72:1996–2005. 2012. View Article : Google Scholar : PubMed/NCBI
86	Culmsee C and Mattson MP: p53 in neuronal apoptosis. Biochem Biophys Res Commun. 331:761–777. 2005. View Article : Google Scholar : PubMed/NCBI
87	Morselli E, Tasdemir E, Maiuri MC, Galluzzi L, Kepp O, Criollo A, Vicencio JM, Soussi T and Kroemer G: Mutant p53 protein localized in the cytoplasm inhibits autophagy. Cell Cycle. 7:3056–3061. 2008. View Article : Google Scholar : PubMed/NCBI
88	Chipuk JE and Green DR: p53's believe it or not: Lessons on transcription-independent death. J Clin Immunol. 23:355–361. 2003. View Article : Google Scholar : PubMed/NCBI
89	Moll UM and Zaika A: Nuclear and mitochondrial apoptotic pathways of p53. FEBS Lett. 493:65–69. 2001. View Article : Google Scholar : PubMed/NCBI
90	Wang EY, Gang H, Aviv Y, Dhingra R, Margulets V and Kirshenbaum LA: p53 mediates autophagy and cell death by a mechanism contingent on Bnip3. Hypertension. 62:70–77. 2013. View Article : Google Scholar : PubMed/NCBI
91	Hendgen-Cotta UB, Esfeld S, Rudi K, Miinalainen I, Klare JP and Rassaf T: Cytosolic BNIP3 dimer interacts with mitochondrial BAX forming heterodimers in the mitochondrial outer membrane under basal conditions. Int J Mol Sci. 18:6872017. View Article : Google Scholar : PubMed/NCBI
92	Namas RA, Metukuri MR, Dhupar R, Velosa C, Jefferson BS, Myer E, Constantine GM, Billiar TR, Vodovotz Y and Zamora R: Hypoxia-induced overexpression of BNIP3 is not dependent on hypoxia-inducible factor 1α in mouse hepatocytes. Shock. 36:196–202. 2011. View Article : Google Scholar : PubMed/NCBI
93	Hanna Akram R: Bnip3 interacts with LC3 to induce selective removal of endoplasmic reticulum and mitochondria via autophagy. UC San Diego Electronic Theses & Dissertations. 12–33. 2011.https://escholarship.org/content/qt1wq0k372/qt1wq0k372.pdfJuly 1–2019
94	Durcan TM and Fon EA: The three ‘P's of mitophagy: PARKIN, PINK1, and post-translational modifications. Genes Dev. 29:989–999. 2015. View Article : Google Scholar : PubMed/NCBI
95	Chen Y and Dorn GW: PINK1-phosphorylated mitofusin 2 is a parkin receptor for culling damaged mitochondria. Science. 340:471–475. 2013. View Article : Google Scholar : PubMed/NCBI
96	Kim-Han J, Kopp S, Dugan L and Diringer M: Perihematomal mitochondrial dysfunction after intracerebral Hemorrhage. Stroke. 37:2457–2462. 2006. View Article : Google Scholar : PubMed/NCBI