Skip to main content
SpringerLink
Log in

Milestones and recent discoveries on cell death mediated by mitochondria and their interactions with biologically active amines

  • Review Article
  • Published:
Amino Acids Aims and scope Submit manuscript

Abstract

Mitochondria represent cell “powerhouses,” being involved in energy transduction from the electrochemical gradient to ATP synthesis. The morphology of their cell types may change, according to various metabolic processes or osmotic pressure. A new morphology of the inner membrane and mitochondrial cristae, significantly different from the previous one, has been proposed for the inner membrane and mitochondrial cristae, based on the technique of electron tomography. Mitochondrial Ca2+ transport (the transporter has been isolated) generates reactive oxygen species and induces the mitochondrial permeability transition of both inner and outer mitochondrial membranes, leading to induction of necrosis and apoptosis. In the mitochondria of several cell types (liver, kidney, and heart), mitochondrial oxidative stress is an essential step in the induction of cell death, although not in brain, in which the phenomenon is caused by a different mechanism. Mitochondrial permeability transition drives both apoptosis and necrosis, whereas mitochondrial outer membrane permeability is characteristic of apoptosis. Adenine nucleotide translocase remains the most important component involved in membrane permeability, with the opening of the transition pore, although other proteins, such as ATP synthase or phosphate carriers, have been proposed. Intrinsic cell death is triggered by the release from mitochondria of proteic factors, such as cytochrome c, apoptosis inducing factor, and Smac/DIABLO, with the activation of caspases upon mitochondrial permeability transition or mitochondrial outer membrane permeability induction. Mitochondrial permeability transition induces the permeability of the inner membrane in sites in contact with the outer membrane; mitochondrial outer membrane permeability forms channels on the outer membrane by means of various stimuli involving Bcl-2 family proteins. The biologically active amines, spermine, and agmatine, have specific functions on mitochondria which distinguish them from other amines. Enzymatic oxidative deamination of spermine by amine oxidases in tumor cells may produce reactive oxygen species, leading to transition pore opening and apoptosis. This process could be exploited as a new therapeutic strategy to combat cancer.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

Abbreviations

ADC:

Arginine decarboxylase

AdNT:

Adenine nucleotide translocase

AGM:

Agmatine

AIF:

Apoptosis-inducing factors

Bak:

Bcl-2 agonist or killer

Bax:

Bcl-2 associated X protein

Bcl-2:

B cell lymphoma 2

BID:

BH3 interacting domain

BSAO:

Bovine serum amine oxidase

CypD:

Cyclophylin D

Cyt.c:

Cytochrome c

FAD:

Flavin adenine dinucleotide

H2O2 :

Hydrogen peroxide

I2 :

Imidazole receptor type 2

IAPs:

Inhibitor of apoptosis proteins

IM:

Inner membrane

MAO:

Monoamine oxidase

MOMP:

Mitochondrial outer membrane permeabilization

MPT:

Mitochondrial permeability transition

MPTP:

Mitochondrial permeability transition pore

OM:

Outer membrane

PAO:

Polyamine oxidase

PUT:

Putrescine

RLM:

Rat liver mitochondria

ROS:

Reactive oxygen species

Smac/DIABLO:

Second mitochondria-derived activator of caspase/direct IAP binding protein with low pI

SMO:

Spermine oxidase

SPD:

Spermidine

SPM:

Spermine

TPP+ :

Tetraphenylphosphonium

VDAC:

Voltage-dependent anion channel

∆E:

Electrode potential variation

∆pH:

Chemical gradient

∆Ψ:

Electrical transmembrane potential

∆µ +H :

Transmembrane electrochemical gradient

References

  • Agostinelli E, Przybytkowski E, Mondovi B, Averill-Bates DA (1994) Heat enhancement of cytotoxicity induced by oxidation products of spermine in Chinese hamster ovary cells. Biochem Pharmacol 48:1181–1186

    Article  CAS  PubMed  Google Scholar 

  • Agostinelli E, Belli F, Molinari A, Condello M, Palmigiani P, Vedova LD, Marra M, Seiler N, Arancia G (2006a) Toxicity of enzymatic oxidation products of spermine to human melanoma cells (M14): sensitisation by heat and MDL 72527. Biochim Biophys Acta 1763:1040–1050

    Article  CAS  PubMed  Google Scholar 

  • Agostinelli E, Dalla Vedova L, Belli F, Condello M, Arancia G, Seiler N (2006b) Sensitization of human colon adenocarcinoma cells (LoVo) to reactive oxygen species by a lysosomotropic compound. Int J Oncol 29:947–955

    CAS  PubMed  Google Scholar 

  • Agostinelli E, Marques MP, Calheiros R, Gil FP, Tempera G, Viceconte N, Battaglia V, Grancara S, Toninello A (2010) Polyamines: fundamental characters in chemistry and biology. Amino Acids 38:393–403

    Article  CAS  PubMed  Google Scholar 

  • Anup R, Madesh M, Balasubramanian KA (1999) Enterocyte mitochondrial dysfunction due to oxidative stress. Indian J Biochem Biophys 36:266–271

    CAS  PubMed  Google Scholar 

  • Arancia G, Calcabrini A, Marra M, Crateri P, Artico M, Martone A, Martelli F, Agostinelli E (2004) Mitochondrial alterations induced by serum amine oxidase and spermine on human multidrug resistant tumor cells. Amino Acids 26:273–282

    Article  CAS  PubMed  Google Scholar 

  • Arnoult D, Parone P, Martinou JC, Antonsson B, Estaquier J, Ameisen JC (2002) Mitochondrial release of apoptosis-inducing factor occurs downstream of cytochrome c release in response to several proapoptotic stimuli. J Cell Biol 159:923–929

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Averill-Bates DA, Chérif A, Agostinelli E, Tanel A, Fortier G (2005) Anti-tumoral effect of native and immobilized bovine serum amine oxidase in a mouse melanoma model. Biochem Pharmacol 69:1693–1704

    Article  CAS  PubMed  Google Scholar 

  • Babal P, Ruchko M, Olson JW, Gillespie MN (2000) Interactions between agmatine and polyamine uptake pathways in rat pulmonary artery endothelial cells. Gen Pharmacol 34:255–261

    Article  CAS  PubMed  Google Scholar 

  • Battaglia V, Rossi CA, Colombatto S, Grillo MA, Toninello A (2007) Different behavior of agmatine in liver mitochondria: inducer of oxidative stress or scavenger of reactive oxygen species? Biochim Biophys Acta 1768:1147–1153

    Article  CAS  PubMed  Google Scholar 

  • Battaglia V, Grancara S, Satriano J, Saccoccio S, Agostinelli E, Toninello A (2010) Agmatine prevents the Ca(2+)-dependent induction of permeability transition in rat brain mitochondria. Amino Acids 38:431–437

    Article  CAS  PubMed  Google Scholar 

  • Bleicken S, Landeta O, Landajuela A, Basañez G, García-Sáez AJ (2013) Proapoptotic Bax and Bak form stable protein-permeable pores of tunable size. J Biol Chem 288:33241–33252

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bonaiuto E, Grancara S, Martinis P, Stringaro A, Colone M, Agostinelli E, Macone A, Stevanato R, Vianello F, Toninello A, Di Paolo ML (2015) A novel enzyme with spermine oxidase properties in bovine liver mitochondria: identification and kinetic characterization. Free Radic Biol Med 81:88–99

    Article  CAS  PubMed  Google Scholar 

  • Bonneau MJ, Poulain R (2000) Spermine oxidation leads to necrosis with plasma membrane phosphatidylserine redistribution in mouse leukemia cells. Exp Cell Res 259:23–34

    Article  CAS  PubMed  Google Scholar 

  • Brenner C, Moulin M (2012) Physiological roles of the permeability transition pore. Circ Res 111:1237–1247

    Article  CAS  PubMed  Google Scholar 

  • Cabella C, Gardini G, Corpillo D, Testore G, Bedino S, Solinas SP, Cravanzola C, Vargiu C, Grillo MA, Colombatto S (2001) Transport and metabolism of agmatine in rat hepatocyte cultures. Eur J Biochem 268:940–947

    Article  CAS  PubMed  Google Scholar 

  • Calcabrini A, Arancia G, Marra M, Crateri P, Befani O, Martone A, Agostinelli E (2002) Enzymatic oxidation products of spermine induce greater cytotoxic effects on human multidrug-resistant colon carcinoma cells (LoVo) than on their wild-type counterparts. Int J Cancer 99:43–52

    Article  CAS  PubMed  Google Scholar 

  • Carafoli E (2003) Historical review: mitochondria and calcium: ups and downs of an unusual relationship. Trends Biochem Sci 28:175–181

    Article  CAS  PubMed  Google Scholar 

  • Carafoli E, Tiozzo R, Lugli G, Crovetti F, Kratzing C (1974) The release of calcium from heart mitochondria by sodium. J Mol Cell Cardiol 6:361–371

    Article  CAS  PubMed  Google Scholar 

  • Cardillo S, De Iuliis A, Battaglia V, Toninello A, Stevanato R, Vianello F (2009) Novel copper amine oxidase activity from rat liver mitochondria matrix. Arch Biochem Biophys 485:97–101

    Article  CAS  PubMed  Google Scholar 

  • Casero RA Jr, Marton LJ (2007) Targeting polyamine metabolism and function in cancer and other hyperproliferative diseases. Nat Rev Drug Discov 6:373–390

    Article  CAS  PubMed  Google Scholar 

  • Chen Y, Kramer DL, Diegelman P, Vujcic S, Porter CW (2001) Apoptotic signaling in polyamine analogue-treated SK-MEL-28 human melanoma cells. Cancer Res 61:6437–6444

    CAS  PubMed  Google Scholar 

  • Dalla Via L, Garcia-Argaez AN, Martinez-Vazquez M, Grancara S, Martinis P, Toninello A (2014) Mitochondrial permeability transition as target of anticancer drugs. Curr Pharm Des 20:223–244

    Article  PubMed  CAS  Google Scholar 

  • De Stefani D, Raffaello A, Teardo E, Szabò I, Rizzuto R (2011) A forty-kilodalton protein of the inner membrane is the mitochondrial calcium uniporter. Nature 476:336–340

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Del Valle AE, Paz JC, Sanchez-Jimenez F, Medina MI (2001) Agmatine uptake by cultured hamster kidney cells. Biochem Biophys Res Commun 280:307–311

    Article  PubMed  CAS  Google Scholar 

  • DeLuca HF, Engstrom GW (1961) Calcium uptake by rat kidney mitochondria. Proc Natl Acad Sci USA 47:1744–1750

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Demers N, Agostinelli E, Averill-Bates DA, Fortier G (2001) Immobilization of native and poly(ethylene glycol)-treated (‘PEGylated’) bovine serum amine oxidase into a biocompatible hydrogel. Biotechnol Appl Biochem 33:201–207

    Article  CAS  PubMed  Google Scholar 

  • Di Noto V, Dalla Via L, Toninello A, Vidali M (1996) Thermodynamic treatment of ligand–receptor interactions. Macromol Theory Simul 5:165–181

    Article  Google Scholar 

  • Di Noto V, Dalla Via L, Zatta P (2002) Review of binding methods and detection of Al(III) binding events in trypsin and DL-DPPC liposomes by a general thermodynamic model. Coord Chem Rev 228:343–363

    Article  Google Scholar 

  • Eisenberg T, Knauer H, Schauer A, Büttner S, Ruckenstuhl C, Carmona-Gutierrez D, Ring J, Schroeder S, Magnes C, Antonacci L, Fussi H, Deszcz L, Hartl R, Schraml E, Criollo A, Megalou E, Weiskopf D, Laun P, Heeren G, Breitenbach M, Grubeck-Loebenstein B, Herker E, Fahrenkrog B, Fröhlich KU, Sinner F, Tavernarakis N, Minois N, Kroemer G, Madeo F (2009) Induction of autophagy by spermidine promotes longevity. Nat Cell Biol 11:1305–1314

    Article  CAS  PubMed  Google Scholar 

  • Fiskum G, Lehninger AL (1979) Regulated release of Ca2+ from respiring mitochondria by Ca2+/2H+ antiport. J Biol Chem 254:6236–6239

    CAS  PubMed  Google Scholar 

  • Frey TG, Mannella CA (2000) The internal structure of mitochondria. Trends Biochem Sci 25:319–324

    Article  CAS  PubMed  Google Scholar 

  • Frey TG, Renken CW, Perkins GA (2002) Insight into mitochondrial structure and function from electron tomography. Biochim Biophys Acta 1555:196–203

    Article  CAS  PubMed  Google Scholar 

  • Gangas JM, Dewey DL (1981) Hog kidney diamine oxidase conversion of biogenic diamines to inhibitors of cell proliferation. J Pathol 134:243–252

    Article  Google Scholar 

  • Gardini G, Cabella C, Cravanzola C, Vargiu C, Belliardo S, Testore G, Solinas SP, Toninello A, Grillo MA, Colombatto S (2001) Agmatine induces apoptosis in rat hepatocyte cultures. J Hepatol 35:482–489

    Article  CAS  PubMed  Google Scholar 

  • Gardini G, Cravanzola C, Autelli R, Testore G, Cesa R, Morando L, Solinas SP, Muzio G, Grillo MA, Colombatto S (2003) Agmatine inhibits the proliferation of rat hepatoma cells by modulation of polyamine metabolism. J Hepatol 39:793–799

    Article  CAS  PubMed  Google Scholar 

  • 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 USA 110:5887–5892

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gogvadze V, Orrenius S, Zhivotovsky B (2006) Multiple pathways of cytochrome c release from mitochondria in apoptosis. Biochim Biophys Acta 1757:639–647

    Article  CAS  PubMed  Google Scholar 

  • Grancara S, Battaglia V, Martinis P, Viceconte N, Agostinelli E, Toninello A, Deana R (2011) Mitochondrial oxidative stress induced by Ca2+ and monoamines: different behaviour of liver and brain mitochondria in undergoing permeability transition. Amino Acids 42:751–759

    Article  PubMed  CAS  Google Scholar 

  • Green DR, Kroemer G (2004) The pathophysiology of mitochondrial cell death. Science 305:626–629

    Article  CAS  PubMed  Google Scholar 

  • Green DR, Reed JC (1998) Mitochondria and apoptosis. Science 281:1309–1312

    Article  CAS  PubMed  Google Scholar 

  • Grijalba MT, Vercesi AE, Schreier S (1999) Ca2+-induced increased lipid packing and domain formation in submitochondrial particles. A possible early step in the mechanism of Ca2+-stimulated generation of reactive oxygen species by the respiratory chain. Biochemistry 38:13279–13287

    Article  CAS  PubMed  Google Scholar 

  • Grundemann D, Hahne C, Berkels R, Schomig E (2003) Agmatine is efficiently transported by non-neuronal monoamine transporters extraneuronal monoamine transporter (EMT) and organic cation transporter 2 (OCT2). J Pharmacol Exp Ther 304:810–817

    Article  CAS  PubMed  Google Scholar 

  • Ha HC, Sirisoma NS, Kuppusamy P, Zweier JL, Woster PM, Casero RA Jr (1998) The natural polyamine spermine functions directly as a free radical scavenger. Proc Natl Acad Sci USA 95:11140–11145

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Haenisch B, Bönisch H, Cichon S, Allam JP, Novak N, Molderings GJ (2011) Effects of exogenous agmatine in human leukemia HMC-1 and HL-60 cells on proliferation, polyamine metabolism and cell cycle. Leuk Res 35:1248–1253

    Article  CAS  PubMed  Google Scholar 

  • Halestrap AP (2005) Biochemistry: a pore way to die. Nature 434:578–579

    Article  CAS  PubMed  Google Scholar 

  • Halestrap AP, Davidson AM (1990) Inhibition of Ca2(+)-induced large-amplitude swelling of liver and heart mitochondria by cyclosporin is probably caused by the inhibitor binding to mitochondrial-matrix peptidyl-prolyl cis-trans isomerase and preventing it interacting with the adenine nucleotide translocase. Biochem J 268:153–160

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Halestrap AP, Woodfield KY, Connern CP (1993) Oxidative stress, thiol reagents, and membrane potential modulate the mitochondrial permeability transition by affecting nucleotide binding to the adenine nucleotide translocase. J Biol Chem 272:3346–3354

    Article  Google Scholar 

  • He X, Duan Y, Yao K, Li F, Hou Y, Wu G, Yin Y (2016) β-Hydroxy-β-methylbutyrate, mitochondrial biogenesis, and skeletal muscle health. Amino Acids 48:653–664

    Article  CAS  PubMed  Google Scholar 

  • Hong S, Kim CY, Lee JE, Seong GJ (2009) Agmatine protects cultured retinal ganglion cells from tumor necrosis factor-alpha-induced apoptosis. Life Sci 84:28–32

    Article  CAS  PubMed  Google Scholar 

  • Hoshino K, Momiyama E, Yoshida K, Nishimura K, Sakai S, Toida T, Kashiwagi K, Igarashi K (2005) Polyamine transport by mammalian cells and mitochondria: role of antizyme and glycosaminoglycans. J Biol Chem 280:42801–42808

    Article  CAS  PubMed  Google Scholar 

  • Keynan O, Mirovsky Y, Dekel S, Gilad VH, Gilad GM (2010) Safety and efficacy of dietary agmatine sulfate in lumbar disc-associated radiculopathy. An open-label, dose-escalating study followed by a randomized, double-blind, placebo-controlled trial. Pain Med 11:356–368

    Article  PubMed  Google Scholar 

  • Kossel A (1910) Über das Agmatin. Zeitschrift für Physiologische Chemie 66:257–261

    Article  Google Scholar 

  • Kowaltowski AJ, Castilho RF, Vercesi AE (2001) Mitochondrial permeability transition and oxidative stress. FEBS Lett 495:12–15

    Article  CAS  PubMed  Google Scholar 

  • Lapidus RG, Sokolove PM (1993) Spermine inhibition of the permeability transition of isolated rat liver mitochondria: an investigation of mechanism. Arch Biochem Biophys 306:246–253

    Article  CAS  PubMed  Google Scholar 

  • Lee J, Giordano S, Zhang J (2012) Autophagy, mitochondria and oxidative stress: cross-talk and redox signalling. Biochem J 441:523–540

    Article  CAS  PubMed  Google Scholar 

  • Lemasters JJ (2005) Selective mitochondrial autophagy, or mitophagy, as a targeted defense against oxidative stress, mitochondrial dysfunction, and aging. Rejuvenation Res 8:3–5

    Article  CAS  PubMed  Google Scholar 

  • Li H, Zhu H, Xu CJ, Yuan J (1998) Cleavage of BID by caspase 8 mediates the mitochondrial damage in the Fas pathway of apoptosis. Cell 94:491–501

    Article  CAS  PubMed  Google Scholar 

  • Lötscher HR, Winterhalter KH, Carafoli E, Richter C (1980) The energy-state of mitochondria during the transport of Ca2+. Eur J Biochem 110:211–216

    Article  PubMed  Google Scholar 

  • Madeo F, Eisenberg T, Büttner S, Ruckenstuhl C, Kroemer G (2010) Spermidine: a novel autophagy inducer and longevity elixir. Autophagy 6:160–162

    Article  PubMed  Google Scholar 

  • Maly DJ (2007) Exploring the intermembrane space. ACS Chem Biol 2:213–216

    Article  CAS  PubMed  Google Scholar 

  • Martinis P, Battaglia V, Grancara S, Dalla Via L, Di Noto V, Saccoccio S, Agostinelli E, Bragadin M, Grillo MA, Toninello A (2012) Further characterization of agmatine binding to mitochondrial membranes: involvement of imidazoline I2 receptor. Amino Acids 42:761–768

    Article  CAS  PubMed  Google Scholar 

  • Minarini A, Zini M, Milelli A, Tumiatti V, Marchetti C, Nicolini B, Falconi M, Farruggia G, Cappadone C, Stefanelli C (2013) Synthetic polyamines activating autophagy: effects on cancer cell death. Eur J Med Chem 67:359–366

    Article  CAS  PubMed  Google Scholar 

  • Molderings GJ, Bonisch H, Gothert M, Bruss M (2001) Agmatine and putrescine uptake in the human glioma cell line SK-MG-1. Naunyn-Schmiedeberg’s Arch Pharmacol 363:671–679

    Article  CAS  Google Scholar 

  • Montanari E, Capece S, Di Meo C, Meringolo M, Coviello T, Agostinelli E, Matricardi P (2013) Hyaluronic acid nanohydrogels as a useful tool for BSAO immobilization in the treatment of melanoma cancer cells. Macromol Biosci 13:1185–1194

    Article  CAS  PubMed  Google Scholar 

  • Moreno-Sánchez R, Hernández-Esquivel L, Rivero-Segura NA, Marín-Hernández A, Neuzil J, Ralph SJ, Rodríguez-Enríquez S (2013) Reactive oxygen species are generated by the respiratory complex II: evidence for lack of contribution of the reverse electron flow in complex I. FEBS J 280:927–938

    PubMed  Google Scholar 

  • Murphy MP (2009) How mitochondria produce reactive oxygen species. Biochem J 417:1–13

    Article  CAS  PubMed  Google Scholar 

  • Nowotarski SL, Woster PM, Casero RA Jr (2013) Polyamines and cancer: implications for chemotherapy and chemoprevention. Expert Rev Mol Med 15:e3

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Osellame LD, Blacker TS, Duchen MR (2012) Cellular and molecular mechanisms of mitochondrial function. Best Pract Res Clin Endocrinol Metab 26:711–723

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Otera H, Ohsakaya S, Nagaura Z, Ishihara N, Mihara K (2005) Export of mitochondrial AIF in response to proapoptotic stimuli depends on processing at the intermembrane space. EMBO J 24:1375–1386

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ott M, Robertson JD, Gogvadze V, Zhivotovsky B, Orrenius S (2001) Cytochrome c release from mitochondria proceeds by a two-step process. Proc Natl Acad Sci USA 99:1259–1263

    Article  CAS  Google Scholar 

  • Palikaras K, Lionaki E, Tavernarakis N (2015) Mitophagy: in sickness and in health. Mol Cell Oncol 3:e1056332

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Pegg AE, Casero RA Jr (2011) Current status of the polyamine research field. Methods Mol Biol 720:3–35

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Perkins G, Renken C, Martone ME, Young SJ, Ellisman M, Frey T (1997) Electron tomography of neuronal mitochondria: three-dimensional structure and organization of cristae and membrane contacts. J Struct Biol 119:260–272

    Article  CAS  PubMed  Google Scholar 

  • Pietrocola F, Lachkar S, Enot DP, Niso-Santano M, Bravo-San Pedro JM, Sica V, Izzo V, Maiuri MC, Madeo F, Mariño G, Kroemer G (2015) Spermidine induces autophagy by inhibiting the acetyltransferase EP300. Cell Death Differ 22:509–516

    Article  CAS  PubMed  Google Scholar 

  • Piletz JE, Aricioglu F, Cheng JT, Fairbanks CA, Gilad VH, Haenisch B, Halaris A, Hong S, Lee JE, Li J, Liu P, Molderings GJ, Rodrigues AL, Satriano J, Seong GJ, Wilcox G, Wu N, Gilad GM (2013) Agmatine: clinical applications after 100 years in translation. Drug Discov Today 18:880–893

    Article  CAS  PubMed  Google Scholar 

  • Raddatz R, Savic SL, Bakthavachalam V, Lesnick J, Jasper JR, McGrath CR, Parini A, Lanier SM (2000) Imidazoline-binding domains on monoamine oxidase B and subpopulations of enzyme. J Pharmacol Exp Ther 292:1135–1145

    CAS  PubMed  Google Scholar 

  • Redmann M, Darley-Usmar V, Zhang J (2016) The role of autophagy, mitophagy and lysosomal functions in modulating bioenergetics and survival in the context of redox and proteotoxic damage: implications for neurodegenerative diseases. Aging Dis 7:150–162

    Article  PubMed  PubMed Central  Google Scholar 

  • Salvi M, Battaglia V, Mancon M, Colombatto S, Cravanzola C, Calheiros R, Marques MP, Grillo MA, Toninello A (2006) Agmatine is transported into liver mitochondria by a specific electrophoretic mechanism. Biochem J 396:337–345

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sava IG, Battaglia V, Rossi CA, Salvi M, Toninello A (2006) Free radical scavenging action of the natural polyamine spermine in rat liver mitochondria. Free Radic Biol Med 41:1272–1281

    Article  CAS  PubMed  Google Scholar 

  • Scheffler IE (2001) Mitochondria make a come back. Adv Drug Deliv Rev 49:3–26

    Article  CAS  PubMed  Google Scholar 

  • Scorrano L (2013) Keeping mitochondria in shape: a matter of life and death. Eur J Clin Invest 43:886–893

    Article  CAS  PubMed  Google Scholar 

  • Siemen D, Ziemer M (2013) What is the nature of the mitochondrial permeability transition pore and what is it not? IUBMB Life 65:255–262

    Article  CAS  PubMed  Google Scholar 

  • Sigrist SJ, Carmona-Gutierrez D, Gupta VK, Bhukel A, Mertel S, Eisenberg T, Madeo F (2014) Spermidine-triggered autophagy ameliorates memory during aging. Autophagy 10:178–179

    Article  CAS  PubMed  Google Scholar 

  • Stefanelli C, Bonavita F, Stanic’ I, Mignani M, Facchini A, Pignatti C, Flamigni F, Caldarera CM (1998) Spermine causes caspase activation in leukaemia cells. FEBS Lett 437:233–236

    Article  CAS  PubMed  Google Scholar 

  • Stefanelli C, Bonavita F, Stanic’ I, Pignatti C, Flamigni F, Guarnieri C, Caldarera CM (1999) Spermine triggers the activation of caspase-3 in a cell-free model of apoptosis. FEBS Lett 451:95–98

    Article  CAS  PubMed  Google Scholar 

  • Stefanelli C, Stanic’ I, Zini M, Bonavita F, Flamigni F, Zambonin L, Landi L, Pignatti C, Guarnieri C, Caldarera CM (2000) Polyamines directly induce release of cytochrome c from heart mitochondria. Biochem J 347:875–880

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Susin SA, Zamzami M, Kroemer G (1998) Mitochondria as regulators of apoptosis: doubt no more. Biochim Biophys Acta 194:1276–1281

    Google Scholar 

  • Tait SW, Green DR (2010) Mitochondria and cell death: outer membrane permeabilization and beyond. Nat Rev Mol Cell Biol 11:621–632

    Article  CAS  PubMed  Google Scholar 

  • Tait SW, Green DR (2012) Mitochondria and cell signalling. J Cell Sci 125:807–815

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Toninello A (2001) Interaction of polyamines with mammalian mitochondria. Curr Top Biochem Res 4:37–48

    CAS  Google Scholar 

  • Toninello A, Di Lisa F, Siliprandi D, Siliprandi N (1984) Protective and restorative effects of spermine in the membrane potential of rat liver mitochondria. In: Caldarera CM, Bachrach U (eds) Advances in polyamines in biomedical science. CLUEB, Bologna, pp 31–67

    Google Scholar 

  • Toninello A, Di Lisa F, Siliprandi D, Siliprandi N (1985) Uptake of spermine by rat liver mitochondria and its influence on the transport of phosphate. Biochim Biophys Acta 815:399–404

    Article  CAS  PubMed  Google Scholar 

  • Toninello A, Miotto G, Siliprandi D, Siliprandi N, Garlid KD (1988) On the mechanism of spermine transport in liver mitochondria. J Biol Chem 263:19407–19411

    CAS  PubMed  Google Scholar 

  • Toninello A, Dalla Via L, Siliprandi D, Garlid KD (1992) Evidence that spermine, spermidine, and putrescine are transported electrophoretically in mitochondria by a specific polyamine uniporter. J Biol Chem 267:18393–18397

    CAS  PubMed  Google Scholar 

  • Toninello A, Salvi M, Mondovì B (2004) Interaction of biologically active amines with mitochondria and their role in the mitochondrial-mediated pathway of apoptosis. Curr Med Chem 11:2349–2374

    Article  CAS  PubMed  Google Scholar 

  • Vahsen N, Candé C, Brière JJ, Bénit P, Joza N, Larochette N, Mastroberardino PG, Pequignot MO, Casares N, Lazar V, Feraud O, Debili N, Wissing S, Engelhardt S, Madeo F, Piacentini M, Penninger JM, Schägger H, Rustin P, Kroemer G (2004) AIF deficiency compromises oxidative phosphorylation. EMBO J 23:4679–4689

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • van Gurp M, Festjens N, van Loo G, Saelens X, Vandenabeele P (2003) Mitochondrial intermembrane proteins in cell death. Biochem Biophys Res Commun 304:487–497

    Article  PubMed  CAS  Google Scholar 

  • Vasington FD, Murphy JV (1962) Ca2+ uptake by rat kidney mitochondria and its dependence on respiration and phosphorylation. J Biol Chem 237:2670–2672

    CAS  PubMed  Google Scholar 

  • Venditti I, Hassanein TF, Fratoddi I, Fontana L, Battocchio C, Rinaldi F, Carafa M, Marianecci C, Diociaiuti M, Agostinelli E, Cametti C, Russo MV (2015) Bioconjugation of gold-polymer core-shell nanoparticles with bovine serum amine oxidase for biomedical applications. Colloids Surf B Biointerfaces 134:314–321

    Article  CAS  PubMed  Google Scholar 

  • Vercesi AE, Kowaltowski AJ, Grijalba MT, Meinicke AR, Castilho RF (1997) The role of reactive oxygen species in mitochondrial permeability transition. Biosci Rep 17:43–52

    Article  CAS  PubMed  Google Scholar 

  • Wallace HM, Fraser AV (2004) Inhibitors of polyamine metabolism: review article. Amino Acids 26:353–365

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

MA wishes to thank Nobile Italia S.p.A. and MB and SM thank Ca’ Foscari University of Venice for financial supports. Thanks are also due to Sapienza University of Rome and to the Italian MIUR (Ministero dell’Istruzione, dell’Università e della Ricerca) for Granting SG (assegno di ricerca), as well as the grant from REGIONE LAZIO Prot. FILAS-RU-2014-1020 is gratefully acknowledged (EA).

Author information

Authors and Affiliations

  1. Department of Biochemical Sciences, University of Rome “La Sapienza”, Piazzale Aldo Moro 5, 00185, Rome, Italy

    Silvia Grancara, Shinji Ohkubo & Enzo Agostinelli

  2. Department of “Organi di Senso”, University of Rome “La Sapienza”, Viale del Policlinico 155, 00161, Rome, Italy

    Marco Artico

  3. Department of Gynecologic-Obstetric and Urological Sciences, University of Rome “La Sapienza”, Viale del Policlinico 155, 00161, Rome, Italy

    Mauro Ciccariello

  4. Department of Molecular Sciences and Nanosystems, Ca’ Foscari University of Venice, Venice, Italy

    Sabrina Manente & Marcantonio Bragadin

  5. Department of Biomedical Sciences, University of Padova, Viale U. Bassi 58B, 35131, Padua, Italy

    Antonio Toninello

  6. Department of Biomedical Sciences, University of Padova, Viale G. Colombo 3, 35131, Padua, Italy

    Antonio Toninello

Authors
  1. Silvia Grancara
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Shinji Ohkubo
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Marco Artico
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Mauro Ciccariello
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Sabrina Manente
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Marcantonio Bragadin
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Antonio Toninello
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Enzo Agostinelli
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Antonio Toninello.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical statement

This research did not involve human participants or animals.

Additional information

Handling Editor: F. Galli.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Grancara, S., Ohkubo, S., Artico, M. et al. Milestones and recent discoveries on cell death mediated by mitochondria and their interactions with biologically active amines. Amino Acids 48, 2313–2326 (2016). https://doi.org/10.1007/s00726-016-2323-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00726-016-2323-z

Keywords

Search

Navigation