Calpeptin, not calpain, directly inhibits an ion channel of the inner mitochondrial membrane
详细信息 查看全文
- 作者：Maria Derksen ; Christian Vorwerk ; Detlef Siemen
- 关键词：Calpain ; Calpeptin ; Calpain inhibitor ; Mitochondria ; Patch clamp ; BK channel ; Permeability transition pore
- 刊名：Protoplasma
- 出版年：2016
- 出版时间：May 2016
- 年：2016
- 卷：253
- 期：3
- 页码：835-843
- 全文大小：582 KB
- 参考文献：Altznauer F, Conus S, Cavalli A, Folkers G, Simon HU (2004) Calpain-1 regulates Bax and subsequent Smac-dependent caspase-3 activation in neutrophil apoptosis. J Biol Chem 279:5947–5957CrossRef PubMed
Andrabi SA, Sayeed I, Siemen D, Wolf G, Horn TF (2004) Direct inhibition of the mitochondrial permeability transition pore: a possible mechanism responsible for anti-apoptotic effects of melatonin. FASEB J 18:869–871PubMed
Bednarczyk P, Wieckowski MR, Broszkiewicz M, Skowronek K, Siemen D, Szewczyk A (2013) Putative structural and functional coupling of the mitochondrial BKCa channel to the respiratory chain. PLoS One 8(6):e68125CrossRef PubMed PubMedCentral
Bernardi P, Di Lisa F, Fogolari F, Lippe G (2015) From ATP to PTP and back: a dual function for the mitochondrial ATP synthase. Circ Res 116:1850–1862CrossRef PubMed
Cao CM, Xia Q, Gao Q, Chen M, Wong TM (2005) Calcium-activated potassium channel triggers cardioprotection of ischemic preconditioning. J Pharmacol Exp Ther 312:644–650CrossRef PubMed
Cheng Y, Gu XQ, Bednarczyk P, Wiedemann FR, Haddad GG, Siemen D (2008) Hypoxia increases activity of the BK-channel in the inner mitochondrial membrane and reduces activity of the permeability transition pore. Cell Physiol Biochem 22:127–136CrossRef PubMed
Cheng Y, Debska-Vielhaber G, Siemen D (2010) Interaction of mitochondrial potassium channels with the permeability transition pore. FEBS Lett 584:2005–2012CrossRef PubMed
Cheng Y, Gulbins E, Siemen D (2011) Activation of the permeability transition pore by Bax via inhibition of the mitochondrial BK channel. Cell Physiol Biochem 27:191–200CrossRef PubMed
Contran N, Cerana R, Crosti P, Malerba M (2007) Cyclosporin A inhibits programmed cell death and cytochrome c release induced by fusicoccin in sycamore cells. Protoplasma 231:193–199CrossRef PubMed
Davies AG, Pierce-Shimomura JT, Kim H, VanHoven MK, Thiele TR, Bonci A, Bargmann CI, McIntire SL (2003) A central role of the BK potassium channel in behavioral responses to ethanol in C. elegans. Cell 115:655–666CrossRef PubMed
Debska-Vielhaber G, Godlewski MM, Kicinska A, Skalska J, Kulawiak B, Piwonska M, Zablocki K, Kunz WS, Szewczyk A, Motyl T (2009) Large-conductance K+ channel openers induce death of human glioma cells. J Physiol Pharmacol 60:27–36PubMed
Dutt P, Spriggs CN, Davies PL, Jia Z, Elce JS (2002) Origins of the difference in Ca2+ requirement for activation of mu- and m-calpain. Biochem J 367:263–269CrossRef PubMed PubMedCentral
Fontaine E, Eriksson O, Ichas F, Bernardi P (1998) Regulation of the permeability transition pore in skeletal muscle mitochondria. Modulation By electron flow through the respiratory chain complex i. J Biol Chem 273:12662–12668CrossRef PubMed
Foster DB, Ho AS, Rucker J, Garlid AO, Chen L, Sidor A, Garlid KD, O’Rourke B (2012) Mitochondrial ROMK channel is a molecular component of mitoK(ATP). Circ Res 111:446–454CrossRef PubMed PubMedCentral
Gao Q, Zhang SZ, Cao CM, Bruce IC, Xia Q (2005) The mitochondrial permeability transition pore and the Ca2 + -activated K+ channel contribute to the cardioprotection conferred by tumor necrosis factor-alpha. Cytokine 32:199–205CrossRef PubMed
Garlid KD (2000) Opening mitochondrial K(ATP) in the heart—what happens, and what does not happen. Basic Res Cardiol 95:275–279CrossRef PubMed
Giorgio V, von Stockum S, Antoniel M, Fabbro A, Fogolari F, Forte M, Glick GD, Petronilli V, Zoratti M, Szabó I, Lippe G, Bernardi P (2013) Dimers of mitochondrial ATP synthase form the permeability transition pore. Proc Natl Acad Sci U S A 110:5887–5892CrossRef PubMed PubMedCentral
Gu XQ, Pamenter ME, Siemen D, Sun X, Haddad GG (2014) Mitochondrial but not plasmalemmal BK channels are hypoxia-sensitive in human glioma. Glia 62:504–513CrossRef PubMed
Gulbins E, Sassi N, Grassmè H, Zoratti M, Szabò I (2010) Role of Kv1.3 mitochondrial potassium channel in apoptotic signalling in lymphocytes. Biochim Biophys Acta 1797:1251–1259CrossRef PubMed
Ichas F, Mazat JP (1998) From calcium signaling to cell death: two conformations for the mitochondrial permeability transition pore. Switching from low- to high-conductance state. Biochim Biophys Acta 1366:33–50CrossRef PubMed
Loupatatzis C, Seitz G, Schönfeld P, Lang F, Siemen D (2002) Single-channel currents of the permeability transition pore from the inner mitochondrial membrane of rat liver and of a human hepatoma cell line. Cell Physiol Biochem 12(5–6):269–278CrossRef PubMed
Parvez S, Winkler-Stuck K, Hertel S, Schönfeld P, Siemen D (2010) The dopamine-D2-receptor agonist ropinirole dose-dependently blocks the Ca2 + -triggered permeability transition of mitochondria. Biochim Biophys Acta 1797:1245–1250CrossRef PubMed
Polster BM, Basañez G, Etxebarria A, Hardwick JM, Nicholls DG (2005) Calpain I induces cleavage and release of apoptosis-inducing factor from isolated mitochondria. J Biol Chem 280:6447–6454CrossRef PubMed
Reverter D, Strobl S, Fernandez-Catalan C, Sorimachi H, Suzuki K, Bode W (2001) Structural basis for possible calcium-induced activation mechanisms of calpains. Biol Chem 382:753–766CrossRef PubMed
Sato T, Saito T, Saegusa N, Nakaya H (2005) Mitochondrial Ca2 + -activated K+ channels in cardiac myocytes: a mechanism of the cardioprotective effect and modulation by protein kinase A. Circulation 111:198–203CrossRef PubMed
Sayeed I, Parvez S, Winkler-Stuck K, Seitz G, Trieu I, Wallesch CW, Schönfeld P, Siemen D (2006) Patch clamp reveals powerful blockade of the mitochondrial permeability transition pore by the D2-receptor agonist pramipexole. FASEB J 20:556–558PubMed
Siemen D, Ziemer M (2013) What is the nature of the mitochondrial permeability transition pore and what is it not? IUBMB Life 65:255–262CrossRef PubMed
Siemen D, Loupatatzis C, Borecky J, Gulbins E, Lang F (1999) Ca2 + -activated K channel of the BK-type in the inner mitochondrial membrane of a human glioma cell line. Biochem Biophys Res Commun 257:549–554CrossRef PubMed
Szabo I, Zoratti M (2014) Mitochondrial channels: ion fluxes and more. Physiol Rev 94:519–608CrossRef PubMed
Wiechelman KJ, Braun RD, Fitzpatrick JD (1988) Investigation of the bicinchoninic acid protein assay: identification of the groups responsible for color formation. Anal Biochem 175:231–237CrossRef PubMed
Xu W, Liu Y, Wang S, McDonald T, Van Eyk JE, Sidor A, O’Rourke B (2002) Cytoprotective role of Ca2 + -activated K+ channels in the cardiac inner mitochondrial membrane. Science 298:1029–1033CrossRef PubMed - 作者单位：Maria Derksen (1)
Christian Vorwerk (2)
Detlef Siemen (1)
1. Department of Neurology, Otto-von-Guericke-Universität, Leipziger Str. 44, D-39120, Magdeburg, Germany
2. Ophthalmology, SRH Zentralklinikum Suhl, D-98527, Suhl, Germany - 刊物类别：Biomedical and Life Sciences
- 刊物主题：Life Sciences
Cell Biology
Plant Sciences
Zoology - 出版者：Springer Wien
- ISSN：1615-6102
文摘
The permeability transition pore (PTP) of inner mitochondrial membranes is a large conductance pathway for ions up to 1500 Da which opening is responsible for ion equilibration and loss of membrane potential in apoptosis and thus in several neurodegenerative diseases. The PTP can be regulated by the Ca2+-activated mitochondrial K channel (BK). Calpains are Ca2+-activated cystein proteases; calpeptin is an inhibitor of calpains. We wondered whether calpain or calpeptin can modulate activity of PTP or BK. Patch clamp experiments were performed on mitoplasts of rat liver (PTP) and of an astrocytoma cell line (BK). Channel-independent open probability (P o) was determined (PTP) and, taking into account the number of open levels, NPo by single channel analysis (BK). We find that PTP in the presence of Ca2+ (200 μM) is uninfluenced by calpain (13 nM) and shows insignificant decrease by the calpain inhibitor calpeptin (1 μM). The NPo of the BK is insensitive to calpain (54 nM), too. However, it is significantly and reversibly inhibited by the calpain inhibitor calpeptin (IC50 = 42 μM). The results agree with calpeptin-induced activation of the PTP via inhibition of the BK. Screening experiments with respirometry show calpeptin effects, fitting to inhibition of the BK by calpeptin, and strong inhibition of state 3 respiration.