The Role of Cardiolipin as a Scaffold Mitochondrial Phospholipid in Autophagosome Formation: In Vitro Evidence
Abstract
:1. Introduction
2. Materials and Methods
2.1. Cells and Autophagy Induction
2.2. Isolation of MAMs
2.3. CL Extraction and Analysis by HPTLC-Immunostaining
2.4. Western Blot Analysis
2.5. Immunoprecipitation Experiments
2.6. Analysis of CL Localization by Scanning Confocal Microscopy
2.7. Statistical Analysis
3. Results
3.1. Cardiolipin Accumulates in MAMs Fractions Following Autophagic Stimulus
3.2. Interaction of Cardiolipin with MFN2 and Calnexin within MAMs
3.3. Cardiolipin Interacts with AMBRA1/BECN1/WIPI1 Complex during Autophagosome Formation
3.4. Cardiolipin Associates with MAM Components during Autophagosome Formation in Neuronal Cells
4. Discussion
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
- Pangborn, M. A simplified preparation of cardiolipin, with a note on purification of lecithin for serologic use. J. Biol. Chem. 1945, 161, 71–82. [Google Scholar] [CrossRef]
- Schlame, M.; Greenberg, M.L. Biosynthesis, remodeling and turnover of mitochondrial cardiolipin. Biochim. Biophys. Acta 2016, 1, 3–7. [Google Scholar] [CrossRef] [Green Version]
- Fiedorczuk, K.; Letts, J.A.; Degliesposti, G.; Kaszuba, K.; Skehel, M.; Sazanov, L.A. Atomic structure of the entire mammalian mitochondrial complex. Nature 2016, 538, 406–410. [Google Scholar] [CrossRef] [Green Version]
- Itoh, K.S.; Aoyama, H.; Muramoto, K.; Terada, H.; Kurauchi, T.; Tadehara, Y.; Yamasaki, A.; Sugimura, T.; Kurono, S.; Tsujimoto, K.; et al. Structures and physiological roles of 13 integral lipids of bovine heart cytochrome c oxidase. EMBO J. 2007, 26, 1713–1725. [Google Scholar] [CrossRef] [PubMed]
- Morelli, A.M.; Ravera, S.; Calzia, D.; Panfoli, I. Hypothesis of lipidphase-continuity proton transfer for aerobic ATP synthesis. J. Cereb. Blood Flow Metab. 2013, 33, 1838–1842. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Ardail, D.; Privat, J.P.; Egret-Charlier, M.; Levrat, C.; Lerme, F.; Louisot, P. Mitochondrial contact sites: Lipid composition and dynamics. J. Biol. Chem. 1990, 265, 18797–18802. [Google Scholar] [CrossRef]
- Reichert, A.S.; Neupert, W. Contact sites between the outer and inner membrane of mitochondria-role in protein transport. Biochim. Biophys. Acta 2002, 1592, 41–49. [Google Scholar] [CrossRef] [Green Version]
- Chu, C.T.; Ji, J.; Dagda, R.K.; Jiang, J.F.; Tyurina, Y.Y.; Kapralov, A.A.; Tyurin, V.A.; Yanamala, N.; Shrivastava, I.H.; Mohammadyani, D.; et al. Cardiolipin externalization to the outer mitochondrial membrane acts as an elimination signal for mitophagy in neuronal cells. Nat. Cell. Biol. 2013, 15, 1197–1205. [Google Scholar] [CrossRef] [Green Version]
- Fernandez, M.G.; Troiano, L.; Moretti, L.; Nasi, M.; Pinti, M.; Salvioli, S.; Dobrucki, J.; Cossarizza, A. Early changes in intramitochondrial cardiolipin distribution during apoptosis. Cell Growth Differ. 2002, 13, 449–455. [Google Scholar]
- Li, X.X.; Tsoi, B.; Li, Y.F.; Kurihara, H.; He, R.R. Cardiolipin and its different properties in mitophagy and apoptosis. J. Histochem. Cytochem. 2015, 63, 301–311. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Kuwana, T.; Mackey, M.R.; Perkins, G.; Ellisman, M.H.; Latterich, M.; Schneiter, R.; Green, D.R.; Newmeyer, D.D. Bid, Bax, and lipids cooperate to form supramolecular openings in the outer mitochondrial membrane. Cell 2002, 111, 331–342. [Google Scholar] [CrossRef] [Green Version]
- Degli Esposti, M.; Cristea, I.M.; Gaskell, S.J.; Nakao, Y.; Dive, C. Proapoptotic Bid binds to monolysocardiolipin, a new molecular connection between mitochondrial membranes and cell death. Cell Death Differ. 2003, 10, 1300–1309. [Google Scholar] [CrossRef] [Green Version]
- Manganelli, V.; Capozzi, A.; Recalchi, S.; Signore, M.; Mattei, V.; Garofalo, T.; Misasi, R.; Degli Esposti, M.; Sorice, M. Altered Traffic of Cardiolipin during Apoptosis: Exposure on the Cell Surface as a Trigger for “Antiphospholipid Antibodies”. J. Immunol. Res. 2015, 2015, 847985. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Sorice, M.; Manganelli, V.; Matarrese, P.; Tinari, A.; Misasi, R.; Malorni, W.; Garofalo, T. Cardiolipin enriched raft-like microdomains are essential activating platforms for apoptotic signals on mitochondria. FEBS Lett. 2009, 583, 2447–2450. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Garofalo, T.; Giammarioli, A.M.; Misasi, R.; Tinari, A.; Manganelli, V.; Gambardella, L.; Pavan, A.; Malorni, W.; Sorice, M. Lipid microdomains contribute to apoptosis-associated modifications of mitochondria in T cells. Cell Death Differ. 2005, 12, 1378–1389. [Google Scholar] [CrossRef]
- Ciarlo, L.; Manganelli, V.; Garofalo, T.; Matarrese, P.; Tinari, A.; Misasi, R.; Malorni, W.; Sorice, M. Association of fission proteins with mitochondrial raft-like domains. Cell Death Differ. 2010, 17, 1047–1058. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Malorni, W.; Giammarioli, A.M.; Garofalo, T.; Sorice, M. Dynamics of lipid raft components during lymphocyte apoptosis: The paradigmatic role of GD3. Apoptosis 2007, 12, 941–949. [Google Scholar] [CrossRef]
- Garofalo, T.; Tinari, A.; Matarrese, P.; Giammarioli, A.M.; Manganelli, V.; Ciarlo, L.; Misasi, R.; Sorice, M.; Malorni, W. Do mitochondria act as ‘cargo boats’ in the journey of GD3 to the nucleus during apoptosis? FEBS Lett. 2007, 581, 3899–3903. [Google Scholar] [CrossRef] [Green Version]
- Degli Esposti, M.; Matarrese, P.; Tinari, A.; Longo, A.; Recalchi, S.; Khosravi-Far, R.; Malorni, W.; Misasi, R.; Garofalo, T.; Sorice, M. Changes in membrane lipids drive increased endocytosis following Fas ligation. Apoptosis 2017, 22, 681–695. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Gonzalvez, F.; Schug, Z.T.; Houtkooper, R.H.; MacKenzie, E.D.; Brooks, D.G.; Wanders, R.J.; Petit, P.X.; Vaz, F.M.; Gottlieb, E. Cardiolipin provides an essential activating platform for caspase-8 on mitochondria. J. Cell Biol. 2008, 183, 681–696. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Klionsky, D.J.; Emr, S.D. Autophagy as a regulated pathway of cellular degradation. Science 2000, 290, 1717–1721. [Google Scholar] [CrossRef]
- Kroemer, G.; Levine, B. Autophagic cell death: The story of a misnomer. Nat. Rev. Mol. Cell Biol. 2008, 9, 1004–1010. [Google Scholar] [CrossRef]
- Todde, V.; Veenhuis, M.M.; van der Klei, I.J. Autophagy: Principles and significance in health and disease. Biochim. Biophys. Acta 2009, 1792, 3–13. [Google Scholar] [CrossRef] [Green Version]
- Levine, B.; Klionsky, D.J. Development by self-digestion: Molecular mechanisms and biological functions of autophagy. Dev. Cell 2004, 6, 463–477. [Google Scholar] [CrossRef]
- Scherz-Shouval, R.; Shvets, E.; Fass, E.; Shorer, H.; Gil, L.; Elazar, Z. Reactive oxygen species are essential for autophagy and specifically regulate the activity of Atg4. EMBO J. 2007, 26, 1749–1760. [Google Scholar] [CrossRef]
- Pelicano, H.; Carney, D.; Huang, P. ROS stress in cancer cells and therapeutic implications. Drug Resist. Update 2004, 7, 97–110. [Google Scholar] [CrossRef]
- Meijer, A.J.; Codogno, P. Regulation and role of autophagy in mammalian cells. Int. J. Biochem. Cell Biol. 2004, 36, 2445–2462. [Google Scholar] [CrossRef] [PubMed]
- Hamasaki, M.; Furuta, N.; Matsuda, A.; Nezu, A.; Yamamoto, A.; Fujita, N.; Oomori, H.; Noda, T.; Haraguchi, T.; Hiraoka, Y.; et al. Autophagosomes form at ER-mitochondria contact sites. Nature 2013, 495, 389–393. [Google Scholar] [CrossRef]
- Kimura, S.; Noda, T.; Yoshimori, T. Dissection of the autophagosome maturation process by a novel reporter protein, tandem fluorescent-tagged LC3. Autophagy 2007, 3, 452–460. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Goni, F.M.; Alonso, A. Effects of ceramide and other simple sphingolipids on membrane lateral structure. Biochim. Biophys. Acta 2009, 1788, 169–177. [Google Scholar] [CrossRef] [Green Version]
- Matarrese, P.; Garofalo, T.; Manganelli, V.; Gambardella, L.; Marconi, M.; Grasso, M.; Tinari, A.; Misasi, R.; Malorni, W.; Sorice, M. Evidence for the involvement of GD3 ganglioside in autophagosome formation and maturation. Autophagy 2014, 10, 750–765. [Google Scholar] [CrossRef]
- Katz, J.; Wals, P.A.; Golden, S.; Raijman, L. Mitochondrial–reticular cytostructure in liver cells. Biochem. J. 1983, 214, 795–813. [Google Scholar] [CrossRef] [Green Version]
- Vance, J.E. MAM (mitochondria-associated membranes) in mammalian cells: Lipids and beyond. Biochim. Biophys. Acta 2014, 1841, 595–609. [Google Scholar] [CrossRef]
- Vance, J.E. Phospholipid synthesis in a membrane fraction associated with mitochondria. J. Biol. Chem. 1990, 265, 7248–7256. [Google Scholar] [CrossRef]
- Levine, T. Short-range intracellular trafficking of small molecules across endoplasmic reticulum junctions. Trends Cell. Biol. 2004, 14, 483–490. [Google Scholar] [CrossRef] [PubMed]
- Sano, R.; Annunziata, I.; Patterson, A.; Moshiach, S.; Gomero, E.; Opferman, J.; Forte, M.; d’Azzo, A. GM1-ganglioside accumulation at the mitochondria-associated ER membranes links ER stress to Ca(2+)-dependent mitochondrial apoptosis. Mol. Cell. 2009, 36, 500–511. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Garofalo, T.; Matarrese, P.; Manganelli, V.; Marconi, M.; Tinari, A.; Gambardella, L.; Faggioni, A.; Misasi, R.; Sorice, M.; Malorni, W. Evidence for the involvement of lipid rafts localized at the ER-mitochondria associated membranes in autophagosome formation. Autophagy 2016, 12, 917–935. [Google Scholar] [CrossRef] [Green Version]
- Poston, C.N.; Duong, E.; Cao, Y.; Bazemore-Walker, C.R. Proteomic analysis of lipid raft-enriched membranes isolated from internal organelles. Biochem. Biophys. Res. Commun. 2011, 415, 355–360. [Google Scholar] [CrossRef] [Green Version]
- Annunziata, I.; Sano, R.; d’Azzo, A. Mitochondria-associated ER membranes (MAMs) and lysosomal storage diseases. Cell Death Dis. 2018, 9, 328. [Google Scholar] [CrossRef] [PubMed]
- Betz, C.; Stracka, D.; Prescianotto-Baschong, C.; Frieden, M.; Demaurex, N.; Hall, M.N. Feature Article: mTOR complex 2-Akt signaling at mitochondria-associated endoplasmic reticulum membranes (MAM) regulates mitochondrial physiology. Proc. Natl. Acad. Sci. USA 2013, 110, 12526–12534. [Google Scholar] [CrossRef] [Green Version]
- Manganelli, V.; Matarrese, P.; Antonioli, M.; Gambardella, L.; Vescovo, T.; Gretzmeier, C.; Longo, A.; Capozzi, A.; Recalchi, S.; Riitano, G.; et al. Raft-like lipid microdomains drive autophagy initiation via AMBRA1-ERLIN1 molecular association within MAMs. Autophagy 2020, 23, 1–21. [Google Scholar] [CrossRef] [PubMed]
- Wieckowski, M.R.; Giorgi, C.; Lebiedzinska, M.; Duszynski, J.; Pinton, P. Isolation of mitochondria-associated membranes and mitochondria from animal tissue and cells. Nat. Protoc. 2009, 4, 1582–1590. [Google Scholar] [CrossRef] [PubMed]
- Conti, F.; Alessandri, C.; Spinelli, F.R.; Capozzi, A.; Martinelli, F.; Recalchi, S.; Misasi, R.; Valesini, G.; Sorice, M. TLC immunostaining for detection of “antiphospholipid” antibodies. Methods Mol. Biol. 2014, 1134, 95–101. [Google Scholar] [PubMed]
- Di Bartolomeo, S.; Corazzari, M.; Nazio, F.; Oliverio, S.; Lisi, G.; Antonioli, M.; Pagliarini, V.; Matteoni, S.; Fuoco, C.; Giunta, L. The dynamic interaction of AMBRA1 with the dynein motor complex regulates mammalian autophagy. J. Cell Biol. 2010, 191, 155–168. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Strappazzon, F.; Nazio, F.; Corrado, M.; Cianfanelli, V.; Romagnoli, A.; Fimia, G.M.; Campello, S.; Nardacci, R.; Piacentini, M.; Campanella, M.; et al. AMBRA1 is able to induce mitophagy via LC3 binding, regardless of PARKIN and p62/SQSTM1. Cell Death Differ. 2015, 22, 419–432. [Google Scholar] [CrossRef] [Green Version]
- Li, J.; Romestaing, C.; Han, X.; Li, Y.; Hao, X.; Wu, Y.; Sun, C.; Liu, X.; Jefferson, L.S.; Xiong, J.; et al. Cardiolipin remodeling by ALCAT1 links oxidative stress and mitochondrial dysfunction to obesity. Cell Metab. 2010, 12, 154–165. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Huang, W.; Choi, W.; Hu, W.; Mi, N.; Guo, Q.; Ma, M.; Liu, M.; Tian, Y.; Lu, P.; Wang, F.L.; et al. Crystal structure and biochemical analyses reveal Beclin 1 as a novel membrane binding protein. Cell Res. 2012, 22, 473–489. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Gilmozzi, V.; Gentile, G.; Castelo Rueda, M.P.; Hicks, A.A.; Pramstaller, P.P.; Zanon, A.; Lévesque, M.; Pichler, I. Interaction of Alpha-Synuclein With Lipids: Mitochondrial Cardiolipin as a Critical Player in the Pathogenesis of Parkinson’s Disease. Front. Neurosci. 2020, 14, 578993. [Google Scholar] [CrossRef] [PubMed]
- Chu, C.T.; Bayır, H.; Kagan, V.E. Autophagy LC3 binds externalized cardiolipin on injured mitochondria to signal mitophagy in neurons: Implications for Parkinson disease. Autophagy 2014, 10, 376–378. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Cai, Q.; Jeong, Y.Y. Mitophagy in Alzheimer’s Disease and Other Age-Related Neurodegenerative Diseases. Cells 2020, 9, 150. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Lou, G.; Palikaras, K.; Lautrup, S.; Scheibye-Knudsen, M.; Tavernarakis, N.; Fang, E.F. Mitophagy and Neuroprotection. Trends Mol. Med. 2020, 26, 8–20. [Google Scholar] [CrossRef] [PubMed]
- Paradies, G.; Paradies, V.; Ruggiero, F.M.; Petrosillo, G. Role of Cardiolipin in Mitochondrial Function and Dynamics in Health and Disease: Molecular and Pharmacological Aspects. Cells 2019, 8, 728. [Google Scholar] [CrossRef] [PubMed] [Green Version]
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Manganelli, V.; Capozzi, A.; Recalchi, S.; Riitano, G.; Mattei, V.; Longo, A.; Misasi, R.; Garofalo, T.; Sorice, M. The Role of Cardiolipin as a Scaffold Mitochondrial Phospholipid in Autophagosome Formation: In Vitro Evidence. Biomolecules 2021, 11, 222. https://doi.org/10.3390/biom11020222
Manganelli V, Capozzi A, Recalchi S, Riitano G, Mattei V, Longo A, Misasi R, Garofalo T, Sorice M. The Role of Cardiolipin as a Scaffold Mitochondrial Phospholipid in Autophagosome Formation: In Vitro Evidence. Biomolecules. 2021; 11(2):222. https://doi.org/10.3390/biom11020222
Chicago/Turabian StyleManganelli, Valeria, Antonella Capozzi, Serena Recalchi, Gloria Riitano, Vincenzo Mattei, Agostina Longo, Roberta Misasi, Tina Garofalo, and Maurizio Sorice. 2021. "The Role of Cardiolipin as a Scaffold Mitochondrial Phospholipid in Autophagosome Formation: In Vitro Evidence" Biomolecules 11, no. 2: 222. https://doi.org/10.3390/biom11020222