PRIN (Italian
Ministry) 2015-2019 - Interfacing organelles and cell physiology
via ion channels: from biophysics to therapy
National coordinator:
Ildiko' Szabo'
Local coordinators: Prof. Vito De Pinto (University of
Catania); Prof. Anna Moroni (University of Milan); Prof. Matteo
Ceccarelli (University of Cagliari); Prof. Armando Carpaneto
(University/CNR of Genova)
Published papers from the project
Unit 1 (UniPD):
1) Bachmann M, Pontarin G, Szabo I. The Contribution of
Mitochondrial Ion Channels to Cancer Development and
Progression. Cell Physiol Biochem. 2019;53(S1):63-78.
2) Paggio A, Checchetto V, Campo A, Menabň R, Di Marco G, Di
Lisa F, Szabo I, Rizzuto R, De Stefani D. Identification of an
ATP-sensitive potassium channel in mitochondria. Nature. 2019
Aug;572(7771):609-613.
3) Costa R, Peruzzo R, Bachmann M, Montŕ GD, Vicario M, Santinon
G, Mattarei A, Moro E, Quintana-Cabrera R, Scorrano L, Zeviani
M, Vallese F, Zoratti M, Paradisi C, Argenton F, Brini M, Calě
T, Dupont S, Szabň I, Leanza L.Impaired Mitochondrial ATP
Production Downregulates Wnt Signaling via ER Stress Induction.
Cell Rep. 2019 Aug 20;28(8):1949-1956.
4) Leanza L, Checchetto V, Biasutto L, Rossa A, Costa R,
Bachmann M, Zoratti M, Szabo I.Pharmacological modulation of
mitochondrial ion channels. Br J Pharmacol. 2019
Nov;176(22):4258-4283.
5) Urbani A, Giorgio V, Carrer A, Franchin C, Arrigoni G, Jiko
C, Abe K, Maeda S, Shinzawa-Itoh K, Bogers JFM, McMillan DGG,
Gerle C, Szabň I, Bernardi P.Purified F-ATP synthase forms a
Ca2+-dependent high-conductance channel matching the
mitochondrial permeability transition pore. Nature Commun. 2019
Sep 25;10(1):4341.
6) Leanza L, Romio M, Becker KA, Azzolini M, Trentin L, Managň
A, Venturini E, Zaccagnino A, Mattarei A, Carraretto L, Urbani
A, Kadow S, Biasutto L, Martini V, Severin F, Peruzzo R,
Trimarco V, Egberts JH, Hauser C, Visentin A, Semenzato G,
Kalthoff H, Zoratti M, Gulbins E, Paradisi C, Szabo I. Direct
Pharmacological Targeting of a Mitochondrial Ion Channel
Selectively Kills Tumor Cells In Vivo. Cancer Cell. 2017 Apr
10;31(4):516-531.e10.
UNIT 2 (UniMi):
1: Alberio L, Locarno A, Saponaro A, Romano E, Bercier V,
Albadri S, Simeoni F,
Moleri S, Pelucchi S, Porro A, Marcello E, Barsotti N, Kukovetz
K, Boender AJ,
Contestabile A, Luo S, Moutal A, Ji Y, Romani G, Beltrame M, Del
Bene F, Di Luca
M, Khanna R, Colecraft HM, Pasqualetti M, Thiel G, Tonini R,
Moroni A. A light-gated potassium channel for sustained neuronal
inhibition. Nature Methods. 2018 Nov;15(11):969-976.
2: Cosentino C, Alberio L, Thiel G, Moroni A. Yeast-Based
Screening System for the Selection of Functional Light-Driven
K+Channels. Methods Mol Biol. 2017;1596:271-285.
3: Saponaro A, Porro A, Chaves-Sanjuan A, Nardini M, Rauh O,
Thiel G, Moroni A.
Fusicoccin Activates KAT1 Channels by Stabilizing Their
Interaction with 14-3-3
Proteins. Plant Cell. 2017 Oct;29(10):2570-2580.
4: Eckert D, Schulze T, Stahl J, Rauh O, Van Etten JL, Hertel B,
Schroeder I,
Moroni A, Thiel G. A small viral potassium ion channel with an
inherent inward
rectification. Channels (Austin). 2019 Dec;13(1):124-135.
5: Rauh O, Urban M, Henkes LM, Winterstein T, Greiner T, Van
Etten JL, Moroni A,
Kast SM, Thiel G, Schroeder I. Identification of Intrahelical
Bifurcated H-Bonds
as a New Type of Gate in K+ Channels. J Am Chem Soc. 2017 Jun
7;139(22):7494-7503.
6: Baumeister D, Hertel B, Schroeder I, Gazzarrini S, Kast SM,
Van Etten JL, Moroni A, Thiel G. Conversion of an instantaneous
activating K+ channel into a slow activating inward rectifier.
FEBS Lett. 2017 Jan;591(2):295-303.
7: Winterstein LM, Kukovetz K, Rauh O, Turman DL, Braun C,
Moroni A, Schroeder
I, Thiel G. Reconstitution and functional characterization of
ion channels from
nanodiscs in lipid bilayers. J Gen Physiol. 2018 Apr
2;150(4):637-646.
UNIT 3 (CNR Genova):
1) Bregante M*, Carpaneto A*, Piazza V, Sbrana F, Vassalli M,
Faimali M, Gambale F. Osmoregulated Chloride Currents in
Hemocytes from Mytilus galloprovincialis. PLoS One (2016)
11(12):e0167972.
2) Lagostena L, Festa M, Pusch M, Carpaneto A. The human
two-pore channel 1 is modulated by cytosolic and luminal
calcium. Sci Rep. (2017) 7:43900.
3) Trost P, Picco C, Scholz-Starke J, Festa M, Lagostena L,
Costa A, Sparla F, Carpaneto A. Electron current recordings in
living cells. Biophys Chem (2017) 229:57-61.
4) Carpaneto A, Boccaccio A, Lagostena L, Di Zanni E,
Scholz-Starke J. The signaling lipid phosphatidylinositol-3,5-bisphosphate
targets plant CLC-a anion/H+ exchange activity. EMBO Rep (2017)
18(7):1100-1107.
5) Pafumi I, Festa M, Papacci F, Lagostena L, Giunta C, Gutla V,
Cornara L, Favia A, Palombi F, Gambale F, Filippini A, Carpaneto
A. Naringenin Impairs Two-Pore Channel 2 Activity And Inhibits
VEGF-Induced Angiogenesis. Sci Rep (2017) 7(1):5121.
6) Carpaneto A, Gradogna A. Modulation of calcium and potassium
permeation in plant TPC channels. Biophys Chem (2018) 236:1-7.
7) Kirsch SA, Kugemann A, Carpaneto A, Böckmann RA, Dietrich P.
Phosphatidylinositol-3,5-bisphosphate lipid-binding-induced
activation of the human two-pore channel 2. Cell Mol Life Sci
(2018) 75(20):3803-3815.
8) Böhm J, Messerer M, Müller HM, Scholz-Starke J, Gradogna A,
Scherzer S, Maierhofer T, Bazihizina N, Zhang H, Stigloher C,
Ache P, Al-Rasheid KAS, Mayer KFX, Shabala S, Carpaneto A,
Haberer G, Zhu JK, Hedrich R. Understanding the Molecular Basis
of Salt Sequestration in Epidermal Bladder Cells of Chenopodium
quinoa. Curr Biol (2018) 28(19):3075-3085.e7.
9) Benkerrou D, Minicozzi V, Gradogna A, Milenkovic S, Bodrenko
IV, Festa M, Lagostena L, Cornara L, D'Amore A, Ceccarelli M,
Filippini A, Carpaneto A. A perspective on the modulation of
plant and animal two pore channels (TPCs) by the flavonoid
naringenin. Biophys Chem (2019) 254:106246.
10) Milenkovic S , Bodrenko IV , Lagostena L , Gradogna A ,
Serra G , Bosin A , Carpaneto A, Ceccarelli M. The mechanism and
energetics of a ligand-controlled hydrophobic gate in a
mammalian two pore channel. Phys Chem Chem Phys (2020)
22(27):15664-15674.
UNIT 4 (UniCa):
1. Guardiani, C. et al. yVDAC2, the second mitochondrial porin
isoform of Saccharomyces cerevisiae. Biochim Biophys Acta 1859,
270–279 (2018).
2.De Pinto, Matteo Ceccarelli, Mariano Andrea Scorciapino, G. M.
I. S. A. M. M. C. V. et al. Folded Structure and Membrane
Affinity of the N‐Terminal Domain of the Three Human Isoforms of
the Mitochondrial Voltage- Dependent Anion-Selective Channel.
ACS Omega 3, 11415–11425 (2018).
3. Vergalli, J. et al. Porins and small-molecule translocation
across the outer membrane of Gram-negative bacteria. Nat Rev
Micro 33, 1831–13 (2019).
4. Coines, J., Acosta-Gutierrez, S., Bodrenko, I., Rovira, C. &
Ceccarelli, M. Glucose transport via the pseudomonad porin OprB:
implications for the design of Trojan Horse anti-infectives.
Phys Chem Chem Phys 14, 529–8463 (2019).
5. Bodrenko, I. V., Salis, S., Acosta-Gutierrez, S. &
Ceccarelli, M. Diffusion of large particles through small pores:
From entropic to enthalpic transport. J Chem Phys 150, 211102
(2019).
6. Moynié, L. et al. The complex of ferric-enterobactin with its
transporter from Pseudomonas aeruginosa suggests a two-site
model. Nature Communications 10, 3673 (2019).
7. Benkerrou, D. et al. A perspective on the modulation of plant
and animal two pore channels (TPCs) by the flavonoid naringenin.
Biophys Chem 254, 106246 (2019).
8. Bafna, J. A. et al. Kanamycin Uptake into Escherichia coli Is
Facilitated by OmpF and OmpC Porin Channels Located in the Outer
Membrane. ACS Infect. Dis. acsinfecdis.0c00102 (2020).
doi:10.1021/acsinfecdis.0c00102
9. Milenkovic, S. et al. The mechanism and energetics of a
ligand-controlled hydrophobic gate in a mammalian two pore
channel. Phys Chem Chem Phys 2004, re15–11 (2020).
UNIT 5 (UniCT):
1) Magrě A, Di Rosa MC, Orlandi I, Guarino F, Reina S,
Guarnaccia M, Morello G, Spampinato A, Cavallaro S, Messina A,
Vai M and De Pinto V. Deletion of Voltage-Dependent Anion
Channel 1 knocks mitochondria down triggering metabolic rewiring
in yeast (2019), Cell Mol Life Sci. doi:
10.1007/s00018-019-03342-8
2) Pittalŕ MGG, Saletti R, Reina S, Cunsolo V, De Pinto V, Foti
S. A High Resolution Mass Spectrometry Study Reveals the
Potential of Disulfide Formation in Human Mitochondrial
Voltage-Dependent Anion Selective Channel Isoforms (hVDACs). Int
J Mol Sci. 2020 Feb 21;21(4):1468.
3) Magrě A, Karachitos A, Di Rosa MC, Reina S, Conti Nibali S,
Messina A, Kmita H, De Pinto V. Recombinant yeast VDAC2: a
comparison of electrophysiological features with the native
form. FEBS Open Bio. 2019 Jul;9(7):1184-1193.
4) Saletti R, Reina S, Pittalŕ MGG, Magrě A, Cunsolo V, Foti S,
De Pinto V. Post-translational modifications of VDAC1 and VDAC2
cysteines from rat liver mitochondria. Biochim Biophys Acta 1859
(2018) 806–816.
5) Magrě A, Reina S, De Pinto V. VDAC1 as Pharmacological Target
in Cancer and Neurodegeneration: Focus on Its Role in Apoptosis.
Front Chem. 2018 6, 108.
6) Guardiani C, Magrě A, Karachitos A, Di Rosa MC, Reina S,
Bodrenko I, Messina A, Kmita H, Ceccarelli M, De Pinto V.
yVDAC2, the second mitochondrial porin isoform of Saccharomyces
cerevisiae. Biochim Biophys Acta. 2018 1859, 4, 270-279.
7) Reina S, De Pinto V. Anti-Cancer Compounds Targeted to VDAC:
Potential and Perspectives. Curr Med Chem. 2017 24, 40,
4447-4469.
8) Saletti R, Cunsolo V, Messina A, De Pinto V, Foti S. High
resolution mass spectrometry characterization of the oxidation
pattern of methionine and cysteine residues in rat liver
mitochondria voltage-dependent anion selective channel 3
(VDAC3). Biochim Biophys Acta. 2017 1859, 301-311.
9) Reina S, Guarino F, Magrě A, De Pinto V. VDAC3 as a potential
marker of mitochondrial status is involved in cancer and
pathology. Front. Oncol., 2016, 6, 264.
10) De Pinto V, Reina S, Gupta A, Messina A, Mahalakshmi R. Role
of cysteines in mammalian VDAC isoforms' function. Biochim
Biophys Acta. 2016, 1857, 789-798.
Human Frontiers Science Program (2015-2019)
Coordinator: ILDIKÓ SZABÓ.
Partners: Giovanni Finazzi (Grenoble, France); Toshiharu Shikanai
(Kyoto, Japan); Chris Chang (Berkeley, USA)
Published papers from the project
Carraretto L., Teardo E., Checchetto V., Finazzi G.*, Uozumi N.*,
Szabň I.* (2016) Ion channels in plant bioenergetic organelles,
chloroplasts and mitochondria: from molecular identification to
function.
Molecular plant, mar 7; 9(3): 371-395
Spetea C., Herdean A., Allorent G., Carraretto L., Finazzi G., Szabň
I.* (2017) An update on the regulation of photosynthesis by
thylakoid ion channels and transporters in
Arabidopsis.
Physiologia plantarum, mar 23. doi: 10.1111/ppl.12568
Wang C., Yamamoto H., Narumiya F., Munekage Y. N., Finazzi G., Szabň
I., Shikanai T.* (2017) Fine-tuned regulation of the K(+) /H(+)
antiporter KEA3 is required to optimize photosynthesis during
induction.
Plant Journal Feb; 89 (3): 540-553
Allorent G., Byrdin M., Carraretto L., Morosinotto T., Szabň I.*,
Finazzi G.* (2018) Global spectroscopic analysis to study the
regulation of the photosynthetic proton motive force: a critical
reappraisal.
Biochimica et Biophysica Acta Bioenergetics, 1859: 676-683
De Bortoli S., Teardo E., Szabň I., Morosinotto T., Alboresi A.
(2016) Evolutionary insight into the ionotropic glutamate receptor
superfamily of photosynthetic organisms.
Biophysical chemistry, nov; 218: 14-26
Sello S., Perotto J., Carraretto L., Szabň I., Vothknecht U. C.,
Navazio L. (2016) Dissecting stimulus-specific Ca2+
signals in amyloplasts and chloroplasts of
Arabidopsis thaliana
cell suspension cultures.
Journal of Experimental Botany, jun; 67 (13): 3965-74
Checchetto V., Teardo E., Carraretto L., Leanza L., Szabo I.* (2016)
Physiology of intracellular potassium channels: a unifying role as
mediators of counterion fluxes?
Biochimica et Biophysica Acta, aug;1857 (8): 1258-1266
Carraretto L., Checchetto V., De Bortoli S., Formentin E., Costa A.,
Szabó I.*, Teardo E.* (2016) Calcium flux across plant mitochondrial
membranes: possible molecular players.
Frontiers in Plant Sciences, mar 31; 7: 354
Checchetto V., Segalla A., Sato Y., Bergantino E., Szabo I.*, Uozumi
N. (2016) Involvement of potassium transport systems in the
response of
Synechocystis
PCC 6803 cyanobacteria to external pH hhange, high-intensity light
stress and heavy metal stress.
Plant & Cell Physiology, apr; 57 (4): 862-77
Herdean A., Teardo E., Nilsson A. K., Pfeil B. E., Johansson O. N.,
Ünnep R., Nagy G., Zsiros O., Dana S., Solymosi K., Garab G., Szabó
I., Spetea C., Lundin B. (2016) A voltage-dependent chloride channel
fine-tunes photosynthesis in plants.
Nature Communications, may 24; 7: 11654
Szabo I.*, Spetea C.* (2017) Impact of the ion transportome of
chloroplasts on the optimization of photosynthesis.
Journal of Experimental Botany, mar 13. doi: 10.1093/jxb/erx063
Spetea C., Szabň I., Kunz H. H. (2017) Editorial: ion transport in
chloroplast and mitochondria physiology in green organisms.
Frontiers in Plant Sciences, jan 5; 7: 2003
Teardo E., Carraretto L., Wagner S., Formentin E., Behera S., De
Bortoli S., Larosa V., Fuchs P., Lo Schiavo F., Raffaello A.,
Rizzuto R., Costa A., Schwarzländer M., Szabň I.* (2017)
Physiological characterization of a plant mitochondrial calcium
uniporter
in vitro
and
in vivo.
Plant physiology, feb; 173 (2): 1355-1370
Costa A., Navazio L., Szabo I.* (2018) The contribution of
organelles to plant intracellular calcium signalling.
Journal of Experimental Botany
Sello S., Moscatiello R., Mehlmer N., Leonardelli M., Carraretto L.,
Cortese E., Zanella F. G., Baldan B., Szabň I., Vothknecht U. C.,
Navazio L. (2018) Chloroplast Ca(2+) fluxes into and across
thylakoids revealed by thylakoid-targeted aequorin probes.
Plant physiology, may; 177 (1): 38-51
Larosa V., Meneghesso A., La Rocca N., Steinbeck J., Hippler M.,
Szabň I., Morosinotto T. (2018) Mitochondria affect photosynthetic
electron transport and photosensitivity in a green alga.
Plant physiology, mar; 176 (3): 2305-2314
Urbani A., Giorgio V., Carrer A., Franchin C., Arrigoni G., Jiko C.,
Abe K., Maeda S., Shinzawa-Itoh K., Bogers J. F. M., McMillan D. G.
G., Gerle C.* Szabň I.*, Bernardi P.* (2019) Purified F-ATP synthase
forms a Ca(2+)-dependent high-conductance channel matching the
mitochondrial permeability transition pore.
Nature communications, sep 25; 10 (1): 4341
Teardo E.+, Carraretto L.+, Moscatiello R.,
Cortese E., Vicario M., Festa M., Maso L., De Bortoli S., Calě T.,
Vothknecht U. C., Formentin E., Cendron L., Navazio L.*, Szabň I.*
(2019) A chloroplast-localized mitochondrial calcium uniporter
transduces osmotic stress in
Arabidopsis.
Nature plants, jun; 5 (6): 581-588
(+Authors sharing first authorship)
Shikanai T., Yamamoto H. (2017) Contribution of cyclic and
pseudo-cyclic electron transport to the formation of proton motive
force in chloroplasts.
Molecular plant 10, 20-29
Kato Y., Sugimoto K., Shikanai T. (2018) NDH-PSI supercomplex
assembly precedes full assembly of the NDH complex in chloroplast.
Plant physiology, 176, 1728-1738
Otani T., Kato Y., Shikanai T. (2018) Specific substitutions of
light-harvesting complex I proteins associated with photosystem I
are required for supercomplex formation with chloroplast NADH
dehydrogenase-like complex.
Plant journal 94, 122-130
Wang C., Takahashi H., Shikanai T. (2018) PROTON GRADIENT REGULATION
5 contributes to ferredoxin-dependent cyclic phosphorylation in
ruptured chloroplasts.
Biochimica et Biophysica Acta Bioenergetics 1859, 1173-1179
Kato Y., Odahara M., Fukao Y., Shikanai T. (2018) Stepwise evolution
of supercomplex formation with photosystem I is required for
stabilization of chloroplast NADH dehydrogenase-like complex:
Lhca5-dependent supercomplex formation in
Physcomitrella patens.
Plant journal 96, 937-948
Nakano H., Yamamoto H., Shikanai T. (2019) Contribution of
NDH-dependent cyclic electron transport around photosystem I to the
generation of proton motive force in the weak mutant allele of pgr5.
Biochimica et Biophysica Acta Bioenergetics 1860, 369-374
Wang C., Shikanai T. (2019) Modification of activity of the
thylakoid H+/K+ antiporter KEA3 disturbs
∆pH-dependent regulation of photosynthesis.
Plant physiology, doi: 10.1104/pp.19.00766
Petroutsos D., Tokutsu R., Maruyama S., Flori S., Greiner A.,
Magneschi L., Cusant L., Kottke T., Mittag M., Hegemann P., Finazzi
G.*, Minagawa J.* (2016) A blue-light photoreceptor mediates the
feedback regulation of photosynthesis.
Nature 537: 563-566
Curien G., Flori S., Villanova V., Magneschi L., Giustini C., Forti
G., Matringe M., Petroutsos D., Kuntz M., Finazzi G.* (2016) The
water to water cycles in microalgae.
Plant & Cell Physiology, jul; 57 (7): 1354-1363
Flori S., Jouneau P. H., Bailleul B., Gallet B., Estrozi L. F.,
Moriscot C., Bastien O., Eicke S., Schober A., Bártulos C. R.,
Maréchal E., Kroth P. G., Petroutsos D., Zeeman S., Breyton C.,
Schoehn G., Falconet D., Finazzi G.* (2017) Plastid thylakoid
architecture optimizes photosynthesis in diatoms.
Nature communications 8: 15885
Villanova V., Fortunato A. E., Singh D., Dal Bo D., Conte M., Obata
T., Jouhet J., Fernie A. R., Marechal E., Falciatore A., Pagliardini
J., Le Monnier A., Poolman M., Curien G., Petroutsos G., Finazzi G.*
(2017) Investigating mixotrophic metabolism in the model diatom
Phaeodactylum tricornutum.
Phil. Trans. R. Soc. B 20160404
Taddei L., Chukhutsina V. U., Lepetit B., Stella G. R., Bassi R.,
Van Amerongen H., Bouly J. P., Jaubert M., Finazzi G., Falciatore A.
(2018) Dynamic changes between two LHCX-related energy quenching
sites control diatom photoacclimation.
Plant physiology 177: 953-965
Allorent G., Guglielmino E., Giustini C., Courtois F. (2018)
Generation of mutants of nuclear-encoded plastid proteins using
CRISPR/Cas9 in the diatom
Phaeodactylum tricornutum.
Methods Molecular Biology 1829: 367-378
Pralon T., Shanmugabalaji V., Longoni P., Glauser G., Ksas B.,
Collombat J., Desmeules S., Havaux M., Finazzi G., Kessler F. (2019)
Plastoquinone homoeostasis by
Arabidopsis
proton gradient regulation 6 is essential for photosynthetic
efficiency.
Communications biology 2019, 2: 220
Decelle J., Stryhanyuk H., Gallet B., Veronesi G., Schmidt M.,
Balzano S., Marro S., Uwizeye C., Jouneau P. H., Lupette J., Jouhet
J., Maréchal E., Schwab Y., Schieber N. L., Tucoulou R., Richnow H.,
Finazzi G., Musat N. (2019) Algal remodeling in an ubiquitous
planktonic photosymbiosis.
Current biology 29: 968-978
Cation homeostasis in chloroplasts
and intracellular signaling (2018-2019)
PI: LUCA CARRARETTO,
STARS (Supporting TAlents in ReSearch) project of the University of
Padova
The principal objects of the project were to start to better
elucidate the role of plastidial ion channels and their involvement
and regulation during stress response and acclimation of
plants/cells. The search for the link between ion channels of
plant bioenergetic organelles and the response of plants to
environmental stresses is still a pioneering branch in plant
physiology, but the knowledge already acquired till now is very
promising. The better understanding of plant response mechanisms
will open new paths in the research to increase resistance to stress
and, therefore, greater plant productivity, useful for food and
industrial purposes.
Published papers from the project
Teardo E.*, Carraretto L.*, Moscatiello R.,
Cortese E., Vicario M., Festa M., Maso L., De Bortoli S., Calě T.,
Vothknecht U. C., Formentin E.+, Cendron L., Navazio L.+,
Szabň I.+ (2019) A chloroplast-localized mitochondrial
calcium uniporter transduces osmotic stress in
Arabidopsis.
Nature plants, jun; 5 (6): 581-588
(* sharing first authorship)
(+ co-corresponding authors) |