VDAC1 Knockout Affects Mitochondrial Oxygen Consumption Triggering a Rearrangement of ETC by Impacting on Complex I Activity
Abstract
:1. Introduction
2. Results
2.1. Characterization of HAP1 ΔVDAC1 Cells
2.2. Deletion of VDAC1 Gene or Inhibition of Its Protein Affects Oxygen Consumption of HAP1 Cells
2.3. VDAC1 Knockout Changes the Contribution of Respiratory States or Complexes to ET Capacity
2.4. Mitochondrial Oxidation of NADH Is Increased in VDAC1 Knockout Cells
2.5. VDAC1 Knockout Makes Cells More Sensitive to Rotenone but Not to Malonic Acid
3. Discussion
4. Materials and Methods
4.1. Cell Lines Maintenance, Proliferation and Treatment
4.2. Western Blotting Analysis
4.3. Cell Viability Assay
4.4. Analysis of Mitochondrial Mass
4.5. High-Resolution Respirometry (HRR)
4.6. Analysis of Respirometric States
4.7. Chromatographic Analysis of Energetic Metabolites
4.8. Determination of Intracellular Lactate
4.9. Statistical Analysis
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
- Shoshan-Barmatz, V.; De Pinto, V.; Zweckstetter, M.; Raviv, Z.; Keinan, N.; Arbel, N. VDAC, a Multi-Functional Mitochondrial Protein Regulating Cell Life and Death. Mol. Asp. Med. 2010, 31, 227–285. [Google Scholar] [CrossRef] [PubMed]
- De Pinto, V. Renaissance of VDAC: New Insights on a Protein Family at the Interface between Mitochondria and Cytosol. Biomolecules 2021, 11, 107. [Google Scholar] [CrossRef] [PubMed]
- Forte, M.; Adelsberger-Mangan, D.; Colombini, M. Purification and Characterization of the Voltage-Dependent Anion Channel from the Outer Mitochondrial Membrane of Yeast. J. Membr. Biol. 1987, 99, 65–72. [Google Scholar] [CrossRef] [PubMed]
- Benz, R.; Wojtczak, L.; Bosch, W.; Brdiczka, D. Inhibition of Adenine Nucleotide Transport through the Mitochondrial Porin by a Synthetic Polyanion. FEBS Lett. 1988, 231, 75–80. [Google Scholar] [CrossRef] [PubMed]
- Nibali, S.C.; Di Rosa, M.C.; Rauh, O.; Thiel, G.; Reina, S.; De Pinto, V. Cell-Free Electrophysiology of Human VDACs Incorporated into Nanodiscs: An Improved Method. Biophys. Rep. 2021, 1, 100002. [Google Scholar] [CrossRef]
- Messina, A.; Reina, S.; Guarino, F.; De Pinto, V. VDAC Isoforms in Mammals. Biochim. Biophys. Acta Biomembr. 2012, 1818, 1466–1476. [Google Scholar] [CrossRef]
- Ujwal, R.; Cascio, D.; Colletier, J.P.; Faham, S.; Zhang, J.; Toro, L.; Ping, P.; Abramson, J. The Crystal Structure of Mouse VDAC1 at 2.3 Å Resolution Reveals Mechanistic Insights into Metabolite Gating. Proc. Natl. Acad. Sci. USA 2008, 105, 17742–17747. [Google Scholar] [CrossRef] [PubMed]
- Hiller, S.; Garces, R.G.; Malia, T.J.; Orekhov, V.Y.; Colombini, M.; Wagner, G. Solution Structure of the Integral Human Membrane Protein VDAC-1 in Detergent Micelles. Science 2008, 321, 1206–1210. [Google Scholar] [CrossRef]
- Bayrhuber, M.; Meins, T.; Habeck, M.; Becker, S.; Giller, K.; Villinger, S.; Vonrhein, C.; Griesinger, C.; Zweckstetter, M.; Zeth, K. Structure of the Human Voltage-Dependent Anion Channel. Proc. Natl. Acad. Sci. USA 2008, 105, 15370–15375. [Google Scholar] [CrossRef]
- Schredelseker, J.; Paz, A.; López, C.J.; Altenbach, C.; Leung, C.S.; Drexler, M.K.; Chen, J.N.; Hubbell, W.L.; Abramson, J. High Resolution Structure and Double Electron-Electron Resonance of the Zebrafish Voltage-Dependent Anion Channel 2 Reveal an Oligomeric Population. J. Biol. Chem. 2014, 289, 12566–12577. [Google Scholar] [CrossRef] [Green Version]
- Manzo, G.; Serra, I.; Magrí, A.; Casu, M.; De Pinto, V.; Ceccarelli, M.; Scorciapino, M.A. 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 2018, 3, 11415–11425. [Google Scholar] [CrossRef]
- De Pinto, V.; Guarino, F.; Guarnera, A.; Messina, A.; Reina, S.; Tomasello, F.M.; Palermo, V.; Mazzoni, C. Characterization of Human VDAC Isoforms: A Peculiar Function for VDAC3? Biochim. Biophys. Acta Bioenerg. 2010, 1797, 1268–1275. [Google Scholar] [CrossRef]
- Benz, R. Permeation of Hydrophilic Solutes through Mitochondrial Outer Membranes: Review on Mitochondrial Porins. BBA—Rev. Biomembr. 1994, 1197, 167–196. [Google Scholar] [CrossRef] [PubMed]
- Rostovtseva, T.; Colombini, M. VDAC Channels Mediate and Gate the Flow of ATP: Implications for the Regulation of Mitochondrial Function. Biophys. J. 1997, 72, 1954–1962. [Google Scholar] [CrossRef] [PubMed]
- Gincel, D.; Shoshan-Barmatz, V. Glutamate Interacts with VDAC and Modulates Opening of the Mitochondrial Permeability Transition Pore. J. Bioenerg. Biomembr. 2004, 36, 179–186. [Google Scholar] [CrossRef]
- Camara, A.K.S.; Zhou, Y.F.; Wen, P.C.; Tajkhorshid, E.; Kwok, W.M. Mitochondrial VDAC1: A Key Gatekeeper as Potential Therapeutic Target. Front. Physiol. 2017, 8, 460. [Google Scholar] [CrossRef] [PubMed]
- Magrì, 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. [Google Scholar] [CrossRef] [PubMed]
- Nakashima, R.A. Hexokinase-Binding Properties of the Mitochondrial VDAC Protein: Inhibition by DCCD and Location of Putative DCCD-Binding Sites. J. Bioenerg. Biomembr. 1989, 21, 461–470. [Google Scholar] [CrossRef] [PubMed]
- Schindler, A.; Foley, E. Hexokinase 1 Blocks Apoptotic Signals at the Mitochondria. Cell. Signal. 2013, 25, 2685–2692. [Google Scholar] [CrossRef]
- Magrì, A.; Belfiore, R.; Reina, S.; Tomasello, M.F.; Di Rosa, M.C.; Guarino, F.; Leggio, L.; De Pinto, V.; Messina, A. Hexokinase i N-Terminal Based Peptide Prevents the VDAC1-SOD1 G93A Interaction and Re-Establishes ALS Cell Viability. Sci. Rep. 2016, 6, 34802. [Google Scholar] [CrossRef] [Green Version]
- Shteinfer-Kuzmine, A.; Argueti, S.; Gupta, R.; Shvil, N.; Abu-Hamad, S.; Gropper, Y.; Hoeber, J.; Magrì, A.; Messina, A.; Kozlova, E.N.; et al. A VDAC1-Derived N-Terminal Peptide Inhibits Mutant SOD1-VDAC1 Interactions and Toxicity in the SOD1 Model of ALS. Front. Cell. Neurosci. 2019, 13, 346. [Google Scholar] [CrossRef]
- Magri, A.; Messina, A. Interactions of VDAC with Proteins Involved in Neurodegenerative Aggregation: An Opportunity for Advancement on Therapeutic Molecules. Curr. Med. Chem. 2017, 24, 4470–4487. [Google Scholar] [CrossRef]
- Reina, S.; De Pinto, V. Anti-Cancer Compounds Targeted to VDAC: Potential and Perspectives. Curr. Med. Chem. 2017, 24, 4447–4469. [Google Scholar] [CrossRef] [PubMed]
- Risiglione, P.; Zinghirino, F.; Di Rosa, M.C.; Magrì, A.; Messina, A. Alpha-Synuclein and Mitochondrial Dysfunction in Parkinson’s Disease: The Emerging Role of VDAC. Biomolecules 2021, 11, 718. [Google Scholar] [CrossRef] [PubMed]
- Cheng, E.H.Y.; Sheiko, T.V.; Fisher, J.K.; Craigen, W.J.; Korsmeyer, S.J. VDAC2 Inhibits BAK Activation and Mitochondrial Apoptosis. Science 2003, 301, 513–517. [Google Scholar] [CrossRef] [PubMed]
- Ma, S.B.; Nguyen, T.N.; Tan, I.; Ninnis, R.; Iyer, S.; Stroud, D.A.; Menard, M.; Kluck, R.M.; Ryan, M.T.; Dewson, G. Bax Targets Mitochondria by Distinct Mechanisms before or during Apoptotic Cell Death: A Requirement for VDAC2 or Bak for Efficient Bax Apoptotic Function. Cell Death Differ. 2014, 21, 1925–1935. [Google Scholar] [CrossRef]
- Chin, H.S.; Li, M.X.; Tan, I.K.L.; Ninnis, R.L.; Reljic, B.; Scicluna, K.; Dagley, L.F.; Sandow, J.J.; Kelly, G.L.; Samson, A.L.; et al. VDAC2 Enables BAX to Mediate Apoptosis and Limit Tumor Development. Nat. Commun. 2018, 9, 4976. [Google Scholar] [CrossRef]
- Reina, S.; Checchetto, V.; Saletti, R.; Gupta, A.; Chaturvedi, D.; Guardiani, C.; Guarino, F.; Scorciapino, M.A.; Magrì, A.; Foti, S.; et al. VDAC3 as a Sensor of Oxidative State of the Intermembrane Space of Mitochondria: The Putative Role of Cysteine Residue Modifications. Oncotarget 2016, 7, 2249–2268. [Google Scholar] [CrossRef]
- Queralt-Martín, M.; Bergdoll, L.; Teijido, O.; Munshi, N.; Jacobs, D.; Kuszak, A.J.; Protchenko, O.; Reina, S.; Magrì, A.; De Pinto, V.; et al. A Lower Affinity to Cytosolic Proteins Reveals VDAC3 Isoform-Specific Role in Mitochondrial Biology. J. Gen. Physiol. 2020, 152, e201912501. [Google Scholar] [CrossRef]
- Saletti, R.; Reina, S.; Pittalà, M.G.G.; Belfiore, 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 Biomembr. 2017, 1859, 301–311. [Google Scholar] [CrossRef]
- Reina, S.; Conti Nibali, S.; Tomasello, M.F.; Magrì, A.; Messina, A.; De Pinto, V. Voltage Dependent Anion Channel 3 (VDAC3) Protects Mitochondria from Oxidative Stress. Redox Biol. 2022, 51, 102264. [Google Scholar] [CrossRef]
- Di Rosa, M.C.; Guarino, F.; Nibali, S.C.; Magrì, A.; De Pinto, V. Voltage-Dependent Anion Selective Channel Isoforms in Yeast: Expression, Structure, and Functions. Front. Physiol. 2021, 12, 675708. [Google Scholar] [CrossRef] [PubMed]
- Magrì, A.; Di Rosa, M.C.; Orlandi, I.; Guarino, F.; Reina, S.; Guarnaccia, M.; Morello, G.; Spampinato, A.; Cavallaro, S.; Messina, A.; et al. Deletion of Voltage-Dependent Anion Channel 1 Knocks Mitochondria down Triggering Metabolic Rewiring in Yeast. Cell. Mol. Life Sci. 2020, 77, 3195–3213. [Google Scholar] [CrossRef] [PubMed]
- Brahimi-Horn, M.C.; Giuliano, S.; Saland, E.; Lacas-Gervais, S.; Sheiko, T.; Pelletier, J.; Bourget, I.; Bost, F.; Féral, C.; Boulter, E.; et al. Knockout of Vdac1 Activates Hypoxia-Inducible Factor through Reactive Oxygen Species Generation and Induces Tumor Growth by Promoting Metabolic Reprogramming and Inflammation. Cancer Metab. 2015, 3, 8. [Google Scholar] [CrossRef] [PubMed]
- Yang, M.; Sun, J.; Stowe, D.F.; Tajkhorshid, E.; Kwok, W.M.; Camara, A.K.S. Knockout of VDAC1 in H9c2 Cells Promotes Oxidative Stress-Induced Cell Apoptosis through Decreased Mitochondrial Hexokinase II Binding and Enhanced Glycolytic Stress. Cell. Physiol. Biochem. 2020, 54, 853–874. [Google Scholar] [CrossRef] [PubMed]
- Essletzbichler, P.; Konopka, T.; Santoro, F.; Chen, D.; Gapp, B.V.; Kralovics, R.; Brummelkamp, T.R.; Nijman, S.M.B.; Bürckstümmer, T. Megabase-Scale Deletion Using CRISPR/Cas9 to Generate a Fully Haploid Human Cell Line. Genome Res. 2014, 24, 2059–2065. [Google Scholar] [CrossRef]
- Pesta, D.; Gnaiger, E. High-Resolution Respirometry: OXPHOS Protocols for Human Cells and Permeabilized Fibers from Small Biopsies of Human Muscle. Methods Mol. Biol. 2012, 810, 25–58. [Google Scholar] [CrossRef]
- Ben-Hail, D.; Begas-Shvartz, R.; Shalev, M.; Shteinfer-Kuzmine, A.; Gruzman, A.; Reina, S.; De Pinto, V.; Shoshan-Barmatz, V. Novel Compounds Targeting the Mitochondrial Protein VDAC1 Inhibit Apoptosis and Protect against Mitochondrial Dysfunction. J. Biol. Chem. 2016, 291, 24986–25003. [Google Scholar] [CrossRef]
- Verma, A.; Pittala, S.; Alhozeel, B.; Shteinfer-Kuzmine, A.; Ohana, E.; Gupta, R.; Chung, J.H.; Shoshan-Barmatz, V. The Role of the Mitochondrial Protein VDAC1 in Inflammatory Bowel Disease: A Potential Therapeutic Target. Mol. Ther. 2022, 30, 726–744. [Google Scholar] [CrossRef] [PubMed]
- Evinova, A.; Cizmarova, B.; Hatokova, Z.; Racay, P. High-Resolution Respirometry in Assessment of Mitochondrial Function in Neuroblastoma SH-SY5Y Intact Cells. J. Memb. Biol. 2020, 253, 129–136. [Google Scholar] [CrossRef]
- Gnaiger, E. Capacity of Oxidative Phosphorylation in Human Skeletal Muscle. New Perspectives of Mitochondrial Physiology. Int. J. Biochem. Cell Biol. 2009, 41, 1837–1845. [Google Scholar] [CrossRef]
- Yang, Y.; Sauve, A.A. NAD+ Metabolism: Bioenergetics, Signaling and Manipulation for Therapy. Biochim. Biophys. Acta Proteins Proteom. 2016, 1864, 1787–1800. [Google Scholar] [CrossRef]
- Sherer, T.B.; Betarbet, R.; Testa, C.M.; Seo, B.B.; Richardson, J.R.; Kim, J.H.; Miller, G.W.; Yagi, T.; Matsuno-Yagi, A.; Greenamyre, J.T. Mechanism of Toxicity in Rotenone Models of Parkinson’s Disease. J. Neurosci. 2003, 23, 10756–10764. [Google Scholar] [CrossRef] [PubMed]
- Gonçalves, R.P.; Buzhynskyy, N.; Prima, V.; Sturgis, J.N.; Scheuring, S. Supramolecular Assembly of VDAC in Native Mitochondrial Outer Membranes. J. Mol. Biol. 2007, 369, 413–418. [Google Scholar] [CrossRef]
- Gonçalves, R.P.; Buzhysnskyy, N.; Scheuring, S. Mini Review on the Structure and Supramolecular Assembly of VDAC. J. Bioenerg. Biomembr. 2008, 40, 133–138. [Google Scholar] [CrossRef]
- Morgenstern, M.; Stiller, S.B.; Lübbert, P.; Peikert, C.D.; Dannenmaier, S.; Drepper, F.; Weill, U.; Höß, P.; Feuerstein, R.; Gebert, M.; et al. Definition of a High-Confidence Mitochondrial Proteome at Quantitative Scale. Cell Rep. 2017, 19, 2836–2852. [Google Scholar] [CrossRef] [PubMed]
- Seitaj, B.; Maull, F.; Zhang, L.; Wüllner, V.; Wolf, C.; Schippers, P.; la Rovere, R.; Distler, U.; Tenzer, S.; Parys, J.B.; et al. Transmembrane BAX Inhibitor-1 Motif Containing Protein 5 (TMBIM5) Sustains Mitochondrial Structure, Shape, and Function by Impacting the Mitochondrial Protein Synthesis Machinery. Cells 2020, 9, 2147. [Google Scholar] [CrossRef]
- Jastroch, M.; Divakaruni, A.S.; Mookerjee, S.; Treberg, J.R.; Brand, M.D. Mitochondrial Proton and Electron Leaks. Essays Biochem. 2010, 47, 53–67. [Google Scholar] [CrossRef]
- Porter, R.K. Mitochondrial Proton Leak: A Role for Uncoupling Proteins 2 and 3? Biochim. Biophys. Acta Bioenerg. 2001, 1504, 120–127. [Google Scholar] [CrossRef] [PubMed]
- Cannon, B.; Shabalina, I.G.; Kramarova, T.V.; Petrovic, N.; Nedergaard, J. Uncoupling Proteins: A Role in Protection against Reactive Oxygen Species-or Not? Biochim. Biophys. Acta Bioenerg. 2006, 1757, 449–458. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Risiglione, P.; Leggio, L.; Cubisino, S.A.M.; Reina, S.; Paternò, G.; Marchetti, B.; Magrì, A.; Iraci, N.; Messina, A. High-Resolution Respirometry Reveals Mpp+ Mitochondrial Toxicity Mechanism in a Cellular Model of Parkinson’s Disease. Int. J. Mol. Sci. 2020, 21, 7809. [Google Scholar] [CrossRef] [PubMed]
- Calabria, E.; Scambi, I.; Bonafede, R.; Schiaffino, L.; Peroni, D.; Potrich, V.; Capelli, C.; Schena, F.; Mariotti, R. Ascs-Exosomes Recover Coupling Efficiency and Mitochondrial Membrane Potential in an in Vitro Model of Als. Front. Neurosci. 2019, 13, 1070. [Google Scholar] [CrossRef]
- Magrì, A.; Risiglione, P.; Caccamo, A.; Formicola, B.; Tomasello, M.F.; Arrigoni, C.; Zimbone, S.; Guarino, F.; Re, F.; Messina, A. Small Hexokinase 1 Peptide against Toxic SOD1 G93A Mitochondrial Accumulation in ALS Rescues the ATP-Related Respiration. Biomedicines 2021, 9, 948. [Google Scholar] [CrossRef] [PubMed]
- Cheng, J.; Nanayakkara, G.; Shao, Y.; Cueto, R.; Wang, L.; Yang, W.Y.; Tian, Y.; Wang, H.; Yang, X. Mitochondrial Proton Leak Plays a Critical Role in Pathogenesis of Cardiovascular Diseases. Adv. Exp. Med. Biol. 2017, 982, 359–370. [Google Scholar] [CrossRef]
- Lemieux, H.; Semsroth, S.; Antretter, H.; Höfer, D.; Gnaiger, E. Mitochondrial Respiratory Control and Early Defects of Oxidative Phosphorylation in the Failing Human Heart. Int. J. Biochem. Cell Biol. 2011, 43, 1729–1738. [Google Scholar] [CrossRef]
- Risiglione, P.; Cubisino, S.A.M.; Lipari, C.L.R.; De Pinto, V.; Messina, A.; Magrì, A. α-Synuclein A53T Promotes Mitochondrial Proton Gradient Dissipation and Depletion of the Organelle Respiratory Reserve in a Neuroblastoma Cell Line. Life 2022, 12, 894. [Google Scholar] [CrossRef]
- Guardiani, C.; Magrì, A.; Karachitos, A.; di Rosa, M.C.; 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 Bioenerg. 2018, 1859, 270–279. [Google Scholar] [CrossRef]
- Magrì, A.; Karachitos, A.; Di Rosa, M.C.; 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, 9, 1184–1193. [Google Scholar] [CrossRef] [PubMed]
- Magrì, A.; Di Rosa, M.C.; Tomasello, M.F.; Guarino, F.; Reina, S.; Messina, A.; De Pinto, V. Overexpression of Human SOD1 in VDAC1-Less Yeast Restores Mitochondrial Functionality Modulating Beta-Barrel Outer Membrane Protein Genes. Biochim. Biophys. Acta Bioenerg. 2016, 1857, 789–798. [Google Scholar] [CrossRef]
- Zinghirino, F.; Pappalardo, X.G.; Messina, A.; Nicosia, G.; De Pinto, V.; Guarino, F. VDAC Genes Expression and Regulation in Mammals. Front. Physiol. 2021, 12, 708695. [Google Scholar] [CrossRef] [PubMed]
- Cesar, M.D.C.; Wilson, J.E. All Three Isoforms of the Voltage-Dependent Anion Channel (VDAC1, VDAC2, and VDAC3) Are Present in Mitochondria from Bovine, Rabbit, and Rat Brain. Arch. Biochem. Biophys. 2004, 422, 191–196. [Google Scholar] [CrossRef] [PubMed]
- Leggio, L.; Guarino, F.; Magrì, A.; Accardi-Gheit, R.; Reina, S.; Specchia, V.; Damiano, F.; Tomasello, M.F.; Tommasino, M.; Messina, A. Mechanism of Translation Control of the Alternative Drosophila Melanogaster Voltage Dependent Anion-Selective Channel 1 MRNAs. Sci. Rep. 2018, 8, 5347. [Google Scholar] [CrossRef] [PubMed]
- Reina, S.; Palermo, V.; Guarnera, A.; Guarino, F.; Messina, A.; Mazzoni, C.; De Pinto, V. Swapping of the N-Terminus of VDAC1 with VDAC3 Restores Full Activity of the Channel and Confers Anti-Aging Features to the Cell. FEBS Lett. 2010, 584, 2837–2844. [Google Scholar] [CrossRef]
- Pronevich, L.A.; Mirzabekov, T.A.; Rozhdestvenskaya, Z.E. Mitochondrial porin regulates the sensitivity of anion carriers to inhibitors. FEBS Lett. 1989, 247, 330–332. [Google Scholar] [CrossRef] [PubMed]
- Leggio, L.; L’episcopo, F.; Magrì, A.; Ulloa-Navas, J.; Paternò, G.; Vivarelli, S.; Bastos, C.A.P.; Tirolo, C.; Testa, N.; Caniglia, S.; et al. Small Extracellular Vesicles Secreted by Nigrostriatal Astrocytes Rescue Cell Death and Preserve Mitochondrial Function in Parkinson’s Disease. Adv. Healthc. Mater. 2022, 11, e2201203. [Google Scholar] [CrossRef]
- Chance, B.; Williams, G.R. Respiratory Enzymes in Oxidative Phosphorylation. III. The Steady State. J. Biol. Chem. 1955, 217, 409–427. [Google Scholar] [CrossRef]
- Bețiu, A.M.; Chamkha, I.; Gustafsson, E.; Meijer, E.; Avram, V.F.; Frostner, E.Å.; Ehinger, J.K.; Petrescu, L.; Muntean, D.M.; Elmér, E. Cell-permeable Succinate Rescues Mitochondrial Respiration in Cellular Models of Amiodarone Toxicity. Int. J. Mol. Sci. 2021, 22, 11786. [Google Scholar] [CrossRef]
- Gnaiger, E. Mitochondrial pathways and respiratory control. An introduction to OXPHOS analysis. Bioenerg. Commun. 2020, 2, 112. [Google Scholar] [CrossRef]
- Lazzarino, G.; Amorini, A.M.; Fazzina, G.; Vagnozzi, R.; Signoretti, S.; Donzelli, S.; di Stasio, E.; Giardina, B.; Tavazzi, B. Single-Sample Preparation for Simultaneous Cellular Redox and Energy State Determination. Anal. Biochem. 2003, 322, 51–59. [Google Scholar] [CrossRef] [PubMed]
- Artiss, J.D.; Karcher, R.E.; Cavanagh, K.T.; Collins, S.L.; Peterson, V.J.; Varma, S.; Zak, B. A Liquid-Stable Reagent for Lactic Acid Levels: Application to the Hitachi 911 and Beckman CX7. Am. J. Clin. Pathol. 2000, 114, 139–143. [Google Scholar] [CrossRef] [PubMed] [Green Version]
Disclaimer/Publisher’s Note: The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content. |
© 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
Share and Cite
Magrì, A.; Cubisino, S.A.M.; Battiato, G.; Lipari, C.L.R.; Conti Nibali, S.; Saab, M.W.; Pittalà, A.; Amorini, A.M.; De Pinto, V.; Messina, A. VDAC1 Knockout Affects Mitochondrial Oxygen Consumption Triggering a Rearrangement of ETC by Impacting on Complex I Activity. Int. J. Mol. Sci. 2023, 24, 3687. https://doi.org/10.3390/ijms24043687
Magrì A, Cubisino SAM, Battiato G, Lipari CLR, Conti Nibali S, Saab MW, Pittalà A, Amorini AM, De Pinto V, Messina A. VDAC1 Knockout Affects Mitochondrial Oxygen Consumption Triggering a Rearrangement of ETC by Impacting on Complex I Activity. International Journal of Molecular Sciences. 2023; 24(4):3687. https://doi.org/10.3390/ijms24043687
Chicago/Turabian StyleMagrì, Andrea, Salvatore Antonio Maria Cubisino, Giuseppe Battiato, Cristiana Lucia Rita Lipari, Stefano Conti Nibali, Miriam Wissam Saab, Alessandra Pittalà, Angela Maria Amorini, Vito De Pinto, and Angela Messina. 2023. "VDAC1 Knockout Affects Mitochondrial Oxygen Consumption Triggering a Rearrangement of ETC by Impacting on Complex I Activity" International Journal of Molecular Sciences 24, no. 4: 3687. https://doi.org/10.3390/ijms24043687