Drp1 regulates mitochondrial dysfunction and dysregulated metabolism in ischemic injury via Clec16a-, BAX-, and GSH- pathways.
Animals
Apoptosis
/ physiology
Autophagosomes
/ metabolism
Cell Line, Tumor
Cytochromes c
/ metabolism
Dynamins
/ metabolism
Glutathione
/ metabolism
Ischemia
/ metabolism
Mitochondria
/ metabolism
Mitochondrial Dynamics
/ physiology
Mitophagy
/ physiology
Rats, Sprague-Dawley
Reperfusion Injury
/ metabolism
Journal
Cell death & disease
ISSN: 2041-4889
Titre abrégé: Cell Death Dis
Pays: England
ID NLM: 101524092
Informations de publication
Date de publication:
20 04 2020
20 04 2020
Historique:
received:
02
12
2019
accepted:
07
04
2020
revised:
06
04
2020
entrez:
22
4
2020
pubmed:
22
4
2020
medline:
30
3
2021
Statut:
epublish
Résumé
The adaptation of mitochondrial homeostasis to ischemic injury is not fully understood. Here, we studied the role of dynamin-related protein 1 (Drp1) in this process. We found that mitochondrial morphology was altered in the early stage of ischemic injury while mitochondrial dysfunction occurred in the late stage of ischemia. Drp1 appeared to inhibit mitophagy by upregulating mito-Clec16a, which suppressed mito-Parkin recruitment and subsequently impaired the formation of autophagosomes in vascular tissues after ischemic injury. Moreover, ischemia-induced Drp1 activation enhanced apoptosis through inducing mitochondrial translocation of BAX and thereby increasing release of Cytochrome C to activate caspase-3/-9 signalling. Furthermore, Drp1 mediated metabolic disorders and inhibited the levels of mitochondrial glutathione to impair free radical scavenging, leading to further increases in ROS and the exacerbation of mitochondrial dysfunction after ischemic injury. Together, our data suggest a critical role for Drp1 in ischemic injury.
Identifiants
pubmed: 32312970
doi: 10.1038/s41419-020-2461-9
pii: 10.1038/s41419-020-2461-9
pmc: PMC7170874
doi:
Substances chimiques
Cytochromes c
9007-43-6
Dnm1l protein, rat
EC 3.6.5.5
Dynamins
EC 3.6.5.5
Glutathione
GAN16C9B8O
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
251Commentaires et corrections
Type : ErratumIn
Références
Vadde, R. et al. Role of hypoxia-inducible factors (HIF) in the maintenance of stemness and malignancy of colorectal cancer. Crit. Rev. Oncol. Hematol. 113, 22–27, https://doi.org/10.1016/j.critrevonc.2017.02.025 (2017).
doi: 10.1016/j.critrevonc.2017.02.025
pubmed: 28427511
Duan, C., Chen, K., Yang, G., Li, T. & Liu, L. HIF-1alpha regulates Cx40-dependent vasodilatation following hemorrhagic shock in rats. Am. J. Transl. Res. 9, 1277–1286 (2017).
pubmed: 28386353
pmcid: 5376018
Liu, Z. Q., Zeng, X. & Duan, C. Y. Neuropsychological rehabilitation and psychotherapy of adult traumatic brain injury patients with depression: a systematic review and meta-analysis. J. Neurosurg. Sci. 62, 24–35, https://doi.org/10.23736/S0390-5616.17.03953-4 (2018).
doi: 10.23736/S0390-5616.17.03953-4
pubmed: 28322535
Mei, Z. B., Duan, C. Y., Li, C. B., Cui, L. & Ogino, S. Prognostic role of tumor PIK3CA mutation in colorectal cancer: a systematic review and meta-analysis. Ann. Oncol. 27, 1836–1848 (2016).
pubmed: 27436848
pmcid: 5035784
Kalogeris, T., Baines, C. P., Krenz, M. & Korthuis, R. J. Ischemia/Reperfusion. Compr. Physiol 7, 113–170 (2016).
pubmed: 28135002
pmcid: 5648017
Duan, C. Y., Zhang, J., Wu, H. L., Li, T. & Liu, L. M. Regulatory mechanisms, prophylaxis and treatment of vascular leakage following severe trauma and shock. Mil. Med. Res. 4, 11 (2017).
pubmed: 28361006
pmcid: 5370457
Duan, C., Yang, G., Li, T. & Liu, L. Advances in vascular hyporeactivity after shock: the mechanisms and managements. Shock 44, 524–534 (2015).
pubmed: 26263436
Chouchani, E. T. et al. Ischaemic accumulation of succinate controls reperfusion injury through mitochondrial ROS. Nature 515, 431–435 (2014).
pubmed: 25383517
pmcid: 4255242
Jawhar, A., Ponelies, N. & Schild, L. Effect of limited ischemia time on the amount and function of mitochondria within human skeletal muscle cells. Eur. J. Trauma Emerg. Surg. 42, 767–773 (2016).
pubmed: 26608839
Wu, Q., Luo, C. L. & Tao, L. Y. Dynamin-related protein 1 (Drp1) mediating mitophagy contributes to the pathophysiology of nervous system diseases and brain injury. Histol. Histopathol. 32, 551–559 (2017).
pubmed: 27830583
Atkins, K., Dasgupta, A., Chen, K. H., Mewburn, J. & Archer, S. L. The role of Drp1 adaptor proteins MiD49 and MiD51 in mitochondrial fission: implications for human disease. Clin. Sci. (Lond.) 130, 1861–1874 (2016).
Kitamura, S. et al. Drp1 regulates mitochondrial morphology and cell proliferation in cutaneous squamous cell carcinoma. J. Dermatol. Sci. 88, 298–307 (2017).
pubmed: 28818497
Shirakabe, A. et al. Drp1-dependent mitochondrial autophagy plays a protective role against pressure overload-induced mitochondrial dysfunction and heart failure. Circulation 133, 1249–1263 (2016).
pubmed: 26915633
pmcid: 4811679
Wada, J. & Nakatsuka, A. Mitochondrial dynamics and mitochondrial dysfunction in diabetes. Acta Med. Okayama 70, 151–158 (2016).
pubmed: 27339203
Xie, Q. et al. Mitochondrial control by DRP1 in brain tumor initiating cells. Nat. Neurosci. 18, 501–510 (2015).
pubmed: 25730670
pmcid: 4376639
Tian, L. et al. Ischemia-induced Drp1 and Fis1-mediated mitochondrial fission and right ventricular dysfunction in pulmonary hypertension. J. Mol. Med. (Berl.) 95, 381–393 (2017).
Duan, C. et al. Activated Drp1-mediated mitochondrial ROS influence the gut microbiome and intestinal barrier after hemorrhagic shock. Aging (Albany NY) https://doi.org/10.18632/aging.102690 (2020).
Li, T. et al. Effects of the balance in activity of RhoA and Rac1 on the shock-induced biphasic change of vascular reactivity in rats. Ann. Surg. 253, 185–193 (2011).
pubmed: 21233615
Xu, J., Yang, G., Li, T. & Liu, L. Myoendothelial gap junctions mediate regulation of angiopoietin-2-induced vascular hyporeactivity after hypoxia through connexin 43-gated cAMP transfer. Am. J. Physiol. Cell Physiol. 313, C262–C273 (2017).
pubmed: 28637680
Miller, L. D. et al. Optimal gene expression analysis by microarrays. Cancer Cell 2, 353–361 (2002).
pubmed: 12450790
Gene Ontology, C. The Gene Ontology (GO) project in 2006. Nucleic Acids Res. 34, D322–326 (2006).
Jolliffe, I. T. & Cadima, J. Principal component analysis: a review and recent developments. Philos. Trans. Ser. A Math. Phys. Eng. Sci. 374, 20150202 (2016).
Hu, H. et al. Acetylation of PGK1 promotes liver cancer cell proliferation and tumorigenesis. Hepatology 65, 515–528 (2017).
pubmed: 27774669
Legesse-Miller, A., Massol, R. H. & Kirchhausen, T. Constriction and Dnm1p recruitment are distinct processes in mitochondrial fission. Mol. Biol. Cell 14, 1953–1963 (2003).
pubmed: 12802067
pmcid: 165089
Ye, R. R., Tan, C. P., Lin, Y. N., Ji, L. N. & Mao, Z. W. A phosphorescent rhenium(I) histone deacetylase inhibitor: mitochondrial targeting and paraptosis induction. Chem. Commun. (Camb.) 51, 8353–8356 (2015).
Li, P. et al. Activation of sirtuin 1/3 improves vascular hyporeactivity in severe hemorrhagic shock by alleviation of mitochondrial damage. Oncotarget 6, 36998–37011 (2015).
pubmed: 26473372
pmcid: 4741911
Lei, Y., Peng, X., Liu, L., Dong, Z. & Li, T. Beneficial effect of cyclosporine A on traumatic hemorrhagic shock. J. Surg. Res. 195, 529–540 (2015).
pubmed: 25752214
Adegoke, E. O. et al. Pharmacological inhibition of TLR4/NF-kappaB with TLR4-IN-C34 attenuated microcystin-leucine arginine toxicity in bovine Sertoli cells. J. Appl. Toxicol. 39, 832–843 (2019).
pubmed: 30671980
Duan, C. et al. miRNA-mRNA crosstalk in myocardial ischemia induced by calcified aortic valve stenosis. Aging 11, 448–466 (2019).
pubmed: 30651404
pmcid: 6366972
Luo, C. Q. et al. Reactive oxygen species-responsive nanoprodrug with quinone methides-mediated GSH depletion for improved chlorambucil breast cancers therapy. J. Control Release 274, 56–68 (2018).
pubmed: 29409835
Buhlman, L. et al. Functional interplay between Parkin and Drp1 in mitochondrial fission and clearance. Biochim. Biophys. Acta 1843, 2012–2026 (2014).
pubmed: 24878071
Soleimanpour, S. A. et al. The diabetes susceptibility gene Clec16a regulates mitophagy. Cell 157, 1577–1590 (2014).
pubmed: 24949970
pmcid: 4184276
Zhang, Y. et al. Acupuncture reduced apoptosis and up-regulated BDNF and GDNF expression in hippocampus following hypoxia-ischemia in neonatal rats. J. Ethnopharmacol. 172, 124–132 (2015).
pubmed: 26116163
Salamon, S. et al. Glucose metabolism in cancer and ischemia: possible therapeutic consequences of the Warburg effect. Nutr. Cancer 69, 177–183 (2017).
pubmed: 28094552
Seidkhani-Nahal, A., Allameh, A. & Soleimani, M. Antioxidant and reactive oxygen species scavenging properties of cellular albumin in HepG2 cells is mediated by the glutathione redox system. Biotechnol. Appl. Biochem. 66, 163–171, (2019).
pubmed: 30402957
Khatkar, S., Nanda, A. & Ansari, S. H. Comparative evaluation of conventional and novel extracts of stem bark of Terminalia arjuna for antihypertensive activity in BSO induced oxidative stress based rat model. Curr. Pharm. Biotechnol. https://doi.org/10.2174/1389201020666190222185209 (2019).
doi: 10.2174/1389201020666190222185209
pubmed: 30963969
Burman, J. L. et al. Mitochondrial fission facilitates the selective mitophagy of protein aggregates. J. Cell Biol. 216, 3231–3247 (2017).
pubmed: 28893839
pmcid: 5626535
Chen, Z. et al. Cardiomyocyte-restricted low density lipoprotein receptor-related protein 6 (LRP6) deletion leads to lethal dilated cardiomyopathy partly through Drp1 signaling. Theranostics 8, 627–643 (2018).
pubmed: 29344294
pmcid: 5771081
Niu, F., Dong, J., Xu, X., Zhang, B. & Liu, B. Mitochondrial division inhibitor 1 prevents early-stage induction of mitophagy and accelerated cell death in a rat model of moderate controlled cortical impact brain injury. World Neurosurg. 122, e1090–e1101 (2019).
pubmed: 30439527
Yan, L. et al. Autophagy in chronically ischemic myocardium. Proc. Natl Acad. Sci. USA 102, 13807–13812 (2005).
pubmed: 16174725
Balduini, W., Carloni, S. & Buonocore, G. Autophagy in hypoxia-ischemia induced brain injury: evidence and speculations. Autophagy 5, 221–223 (2009).
pubmed: 19029804
Carloni, S., Buonocore, G. & Balduini, W. Protective role of autophagy in neonatal hypoxia-ischemia induced brain injury. Neurobiol. Dis. 32, 329–339 (2008).
pubmed: 18760364
Carloni, S., Buonocore, G., Longini, M., Proietti, F. & Balduini, W. Inhibition of rapamycin-induced autophagy causes necrotic cell death associated with Bax/Bad mitochondrial translocation. Neuroscience 203, 160–169, (2012).
pubmed: 22209856
Wen, Y. D. et al. Neuronal injury in rat model of permanent focal cerebral ischemia is associated with activation of autophagic and lysosomal pathways. Autophagy 4, 762–769 (2008).
pubmed: 18567942
Zhang, X. et al. Cerebral ischemia-reperfusion-induced autophagy protects against neuronal injury by mitochondrial clearance. Autophagy 9, 1321–1333 (2013).
pubmed: 23800795
Matsui, Y. et al. Distinct roles of autophagy in the heart during ischemia and reperfusion: roles of AMP-activated protein kinase and Beclin 1 in mediating autophagy. Circ. Res. 100, 914–922 (2007).
pubmed: 17332429
Cheng, X. et al. Pacer is a mediator of mTORC1 and GSK3-TIP60 signaling in regulation of autophagosome maturation and lipid metabolism. Mol. Cell 73, 788–802 e787 (2019).
pubmed: 30704899
Ginet, V., Puyal, J., Clarke, P. G. & Truttmann, A. C. Enhancement of autophagic flux after neonatal cerebral hypoxia-ischemia and its region-specific relationship to apoptotic mechanisms. Am. J. Pathol. 175, 1962–1974 (2009).
pubmed: 19815706
pmcid: 2774060
Sheng, R. & Qin, Z. H. The divergent roles of autophagy in ischemia and preconditioning. Acta Pharm. Sin. 36, 411–420, https://doi.org/10.1038/aps.2014.151 (2015).
doi: 10.1038/aps.2014.151
Cui, D. R. et al. Propofol prevents cerebral ischemia-triggered autophagy activation and cell death in the rat hippocampus through the NF-kappaB/p53 signaling pathway. Neuroscience 246, 117–132 (2013).
pubmed: 23644056
Xia, D. Y. et al. 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).
pubmed: 23903681
pmcid: 3859329
Li, W. L. et al. The regulatory role of NF-kappaB in autophagy-like cell death after focal cerebral ischemia in mice. Neuroscience 244, 16–30 (2013).
pubmed: 23558089
pmcid: 3916093
Qin, A. P. et al. Autophagy was activated in injured astrocytes and mildly decreased cell survival following glucose and oxygen deprivation and focal cerebral ischemia. Autophagy 6, 738–753 (2010).
pubmed: 20574158
Yen, J. H., Huang, H. S., Chuang, C. J. & Huang, S. T. Activation of dynamin-related protein 1-dependent mitochondria fragmentation and suppression of osteosarcoma by cryptotanshinone. J. Exp. Clin. Cancer Res. 38, 42 (2019).
pubmed: 30691497
pmcid: 6350405
Eltzschig, H. K. & Eckle, T. Ischemia and reperfusion–from mechanism to translation. Nat. Med. 17, 1391–1401 (2011).
pubmed: 22064429
Park, S. W., Kim, M., Brown, K. M., D’Agati, V. D. & Lee, H. T. Paneth cell-derived interleukin-17A causes multiorgan dysfunction after hepatic ischemia and reperfusion injury. Hepatology 53, 1662–1675 (2011).
pubmed: 21360570
pmcid: 3082595
Hotchkiss, R. S., Strasser, A., McDunn, J. E. & Swanson, P. E. Cell death. N. Engl. J. Med. 361, 1570–1583 (2009).
pubmed: 19828534
pmcid: 3760419
Ogawa, S. et al. Hypoxia-induced increased permeability of endothelial monolayers occurs through lowering of cellular cAMP levels. Am. J. Physiol. 262, C546–554 (1992).
pubmed: 1312775
Eltzschig, H. K. & Carmeliet, P. Hypoxia and inflammation. N. Engl. J. Med. 364, 656–665 (2011).
pubmed: 21323543
pmcid: 3930928
Semenza, G. L. Life with oxygen. Science 318, 62–64 (2007).
pubmed: 17916722
Miller, E. J. et al. Macrophage migration inhibitory factor stimulates AMP-activated protein kinase in the ischaemic heart. Nature 451, 578–582 (2008).
pubmed: 18235500
Matsuo, K., Yabuki, Y. & Fukunaga, K. Combined l-citrulline and glutathione administration prevents neuronal cell death following transient brain ischemia. Brain Res. 1663, 123–131 (2017).
pubmed: 28315310