Metabolic Shifts as the Hallmark of Most Common Diseases: The Quest for the Underlying Unity
Abstract
:1. Introduction
2. Cells Proliferate under Redox Conditions and Differentiate from Oxidation
3. Metabolic Shifts in a Broad Spectrum of Diseases
4. Inflammation in a Broad Spectrum of Diseases
Organ | Disease | Inflammation | Mitochondrial Impairment | Lactic Acid Concentration |
---|---|---|---|---|
Brain | Autism | Yes | Yes [58] | Increased [59] |
Schizophrenia | Yes | Yes [58] | Increased [60] | |
Meningitis | Yes | Yes [61] | Increased [60] | |
Encephalitis | Yes | Yes [62] | Increased [63] | |
Alzheimer | Yes | Yes [27] | Increased [27] | |
Parkinson | Yes | Yes [64] | Stable under treatment [65] | |
Huntington | Yes | Yes [66] | Increased [67] | |
Cardio-vascular | Cardiac infract | Yes: scarring | Yes [68] | Increased [69] |
Cardiac failure | Yes | Yes [70] | Increased [69] | |
Stroke | Yes: scarring | Yes [71] | Increased [72] | |
Bronchia alveolar | Infection | Yes | Yes [73] | Not available |
Fibrosis | Yes | Yes [74] | Increased [75] | |
Emphysema | Yes | Yes [76] | Increased [77] | |
Cancer | Yes | Yes [27] | Increased [27] | |
Joint and muscular | Arthritis | Yes | Yes [78] | Increased [77] |
Myositis | Yes | Yes [79] | Not available | |
Sarcoma | Yes | Yes [27] | Increased [27] | |
GI tract | Hepatitis | Yes | Yes [80] | Increased [80] |
Cirrhosis | Yes | Yes [81] | Increased [82] | |
ulcerative colitis | Yes | Yes [83] | Increased [84] | |
Urinary tract | Cystitis | Yes | Yes [85] | Increased [86] |
Cancer | Yes | Yes [27] | Increased [27] | |
Autoimmune disease | Scleroderma | Yes | Yes [87] | Not available |
Lupus | Yes | Yes [88] | Increased [89] | |
Sarcoidosis | Yes | Yes [90] | Increased [91] | |
Down’ syndrome | Diffuse | Yes | Yes [92] | Increased [93] |
Cystic fibrosis | Lung and GI tract | Yes | Yes [94] | Increased [95] |
Aging | Diffuse | Yes | Yes [27] | Increased [27] |
5. Inflammation Is Responsible for Metabolic Shifts
6. Intracellular pH and the Consequence of the Metabolic Shifts
7. Conclusions: Handling the Complexity of Phenotypes in a Single Frame
Author Contributions
Funding
Conflicts of Interest
References
- Henry, M.; Schwartz, L. Entropy export as the driving force of evolution. Substantia 2019, 3, 29–56. [Google Scholar] [CrossRef]
- Schwartz, L.; Devin, A.; Bouillaud, F.; Henry, M. Entropy as the Driving Force of Pathogenesis: An Attempt of Diseases Classification Based on the Laws of Physics. Substantia 2020, 4. [Google Scholar] [CrossRef]
- Henry, M. Thermodynamics of Life. Substantia 2020, 5, 43–71. [Google Scholar] [CrossRef]
- Lehninger, A.L. Bioenergetics: The Molecular Basis of Biological Energy Transformations; Benjamin-Cummings Publishing Company: San Francisco, CA, USA, 1965. [Google Scholar]
- Peregrín-Alvarez, J.M.; Sanford, C.; Parkinson, J. The conservation and evolutionary modularity of metabolism. Genome Biol. 2009, 10. [Google Scholar] [CrossRef] [Green Version]
- Demetrius, L. Cellular systems as graphs. Bull. Math. Biophys. 1968, 30, 105–116. [Google Scholar] [CrossRef] [PubMed]
- Schwartz, L.; da Veiga Moreira, J.; Jolicoeur, M. Physical forces modulate cell differentiation and proliferation processes. J. Cell. Mol. Med. 2018, 22, 738–745. [Google Scholar] [CrossRef] [Green Version]
- McBride, H.M.; Neuspiel, M.; Wasiak, S. Mitochondria: More Than Just a Powerhouse. Curr. Biol. 2006, 16, R551–R560. [Google Scholar] [CrossRef] [Green Version]
- Laflaquière, B.; Leclercq, G.; Choey, C.; Chen, J.; Peres, S.; Ito, C.; Jolicoeur, M. Identifying biomarkers of Wharton’s Jelly mesenchymal stromal cells using a dynamic metabolic model: The cell passage effect. Metabolites 2018, 8, 18. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- John, C.S.J.; Ramalho-Santos, J.; Gray, H.L.; Petrosko, P.; Rawe, V.Y.; Navara, C.S.; Simerly, C.R.; Schatten, G.P. The expression of mitochondrial DNA transcription factors during early cardiomyocyte in vitro differentiation from human embryonic stemn cells. Cloning Stem Cells 2005, 7, 141–153. [Google Scholar] [CrossRef]
- Mandal, S.; Lindgren, A.G.; Srivastava, A.S.; Clark, A.T.; Banerjee, U. Mitochondrial function controls proliferation and early differentiation potential of embryonic stem cells. Stem Cells 2011, 29, 486–495. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Wanet, A.; Arnould, T.; Najimi, M.; Renard, P. Connecting Mitochondria, Metabolism, and Stem Cell Fate. Stem Cells Dev. 2015, 24, 1957–1971. [Google Scholar] [CrossRef] [Green Version]
- Levenson, R.; Macara, I.G.; Smith, R.L.; Cantley, L.; Housman, D. Role of mitochondrial membrane potential in the regulation of murine erythroleukemia cell differentiation. Cell 1982, 28, 855–863. [Google Scholar] [CrossRef]
- Buck, M.D.D.; O’Sullivan, D.; Klein Geltink, R.I.I.; Curtis, J.D.D.; Chang, C.H.; Sanin, D.E.E.; Qiu, J.; Kretz, O.; Braas, D.; van der Windt, G.J.J.W.; et al. Mitochondrial Dynamics Controls T Cell Fate through Metabolic Programming. Cell 2016, 166, 63–76. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Pearce, E.L.; Poffenberger, M.C.; Chang, C.-H.; Jones, R.G. Fueling immunity: Insights into metabolism and lymphocyte function. Science 2013, 342, 1242454. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Kasahara, A.; Scorrano, L. Mitochondria: From cell death executioners to regulators of cell differentiation. Trends Cell Biol. 2014, 24, 761–770. [Google Scholar] [CrossRef] [PubMed]
- Zhang, Y.; Marsboom, G.; Toth, P.T.; Rehman, J. Mitochondrial Respiration Regulates Adipogenic Differentiation of Human Mesenchymal Stem Cells. PLoS ONE 2013, 8. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Da Veiga Moreira, J.; Peres, S.; Steyaert, J.-M.M.; Bigan, E.; Paulevé, L.; Nogueira, M.L.; Schwartz, L. Cell cycle progression is regulated by intertwined redox oscillators. Theor. Biol. Med. Model. 2015, 12, 10. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Da Veiga Moreira, J.; Hamraz, M.; Abolhassani, M.; Bigan, E.; Pérès, S.; Paulevé, L.; Nogueira, M.L.; Steyaert, J.-M.; Schwartz, L. The Redox Status of Cancer Cells Supports Mechanisms behind the Warburg Effect. Metabolites 2016, 6, 33. [Google Scholar] [CrossRef]
- Alfarouk, K.O.; Ahmed, S.B.M.; Elliott, R.L.; Benoit, A.; Alqahtani, S.S.; Ibrahim, M.E.; Bashir, A.H.H.; Alhoufie, S.T.S.; Elhassan, G.O.; Wales, C.C.; et al. The Pentose Phosphate Pathway Dynamics in Cancer and Its Dependency on Intracellular pH. Metabolites 2020, 10, 285. [Google Scholar] [CrossRef]
- Chiche, J.; Ilc, K.; Laferrière, J.; Trottier, E.; Dayan, F.; Mazure, N.M.; Brahimi-Horn, M.C.; Pouysségur, J. Hypoxia-inducible carbonic anhydrase IX and XII promote tumor cell growth by counteracting acidosis through the regulation of the intracellular pH. Cancer Res. 2009, 69, 358–368. [Google Scholar] [CrossRef] [Green Version]
- McCully, K.K.; Fielding, R.A.; Evans, W.J.; Leigh, J.S.; Posner, J.D. Relationships between in vivo and in vitro measurements of metabolism in young and old human calf muscles. J. Appl. Physiol. 1993, 75, 813–819. [Google Scholar] [CrossRef]
- Wertz, X.; Schoëvaërt, D.; Maitournam, H.; Chassignet, P.; Schwartz, L. The effect of hormones on bone growth is mediated through mechanical stress. Comptes Rendus-Biol. 2006, 329, 79–85. [Google Scholar] [CrossRef]
- Zhang, P.C.; Keleshian, A.M.; Sachs, F. Voltage-induced membrane movement. Nature 2001, 413, 428–432. [Google Scholar] [CrossRef]
- Ames, B.N.; Liu, J.; Atamna, H.; Hagen, T.M. Delaying the mitochondrial decay of aging in the brain. Clin. Neurosci. Res. 2003, 2, 331–338. [Google Scholar] [CrossRef]
- Seyfried, T.N.; Flores, R.E.; Poff, A.M.; D’Agostino, D.P. Cancer as a metabolic disease: Implications for novel therapeutics. Carcinogenesis 2014, 35, 515–527. [Google Scholar] [CrossRef]
- Schwartz, L.; Peres, S.; Jolicoeur, M.; da Veiga Moreira, J. Cancer and Alzheimer’s disease: Intracellular pH scales the metabolic disorders. Biogerontology 2020, 21, 683–694. [Google Scholar] [CrossRef]
- Fitzgerald, P.J. Norepinephrine release may play a critical role in the Warburg effect: An integrative model of tumorigenesis. Neoplasma 2020. [Google Scholar] [CrossRef]
- Altschule, M.D.; Henneman, D.H.; Holliday, P.; Goncz, R.M. Carbohydrate Metabolism in Brain Disease: VI. Lactate Metabolism after Infusion of Sodium d-Lactate in Manic-Depressive and Schizophrenic Psychoses. AMA Arch. Intern. Med. 1956, 98, 35–38. [Google Scholar] [CrossRef] [PubMed]
- Pitts, F.N.; McClure, J.N. Lactate metabolism in anxiety neurosis. N. Engl. J. Med. 1967, 277, 1329–1336. [Google Scholar] [CrossRef] [PubMed]
- Liebowitz, M.R.; Hollander, E. Lactate-induced anxiety. Biol. Psychiatry 1989, 25, 669–670. [Google Scholar] [CrossRef]
- Hollander, E.; Liebowitz, M.R.; Gorman, J.M.; Cohen, B.; Fyer, A.; Klein, D.F. Cortisol and Sodium Lactate—Induced Panic. Arch. Gen. Psychiatry 1989, 46, 135–140. [Google Scholar] [CrossRef]
- Reiman, E.M.; Raichle, M.E.; Robins, E.; Mintun, M.A.; Fusselman, M.J.; Fox, P.T.; Price, J.L.; Hackman, K.A. Neuroanatomical Correlates of a Lactate-Induced Anxiety Attack. Arch. Gen. Psychiatry 1989, 46, 493–500. [Google Scholar] [CrossRef] [PubMed]
- Mostafa, G.A.; El-Gamal, H.A.; El-Wakkad, A.S.E.; El-Shorbagy, O.E.; Hamza, M.M. Polyunsaturated fatty acids, carnitine and lactate as biological markers of brain energy in autistic children. Int. J. Child Neuropsychiatry 2005, 2, 179–188. [Google Scholar]
- Yehia, L.; Ni, Y.; Feng, F.; Seyfi, M.; Sadler, T.; Frazier, T.W.; Eng, C. Distinct Alterations in Tricarboxylic Acid Cycle Metabolites Associate with Cancer and Autism Phenotypes in Cowden Syndrome and Bannayan-Riley-Ruvalcaba Syndrome. Am. J. Hum. Genet. 2019, 105, 813–821. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Goh, S.; Dong, Z.; Zhang, Y.; DiMauro, S.; Peterson, B.S. Mitochondrial dysfunction as a neurobiological subtype of autism spectrum disorder: Evidence from brain imaging. JAMA Psychiatry 2014, 71, 665–671. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Regenold, W.T.; Phatak, P.; Marano, C.M.; Sassan, A.; Conley, R.R.; Kling, M.A. Elevated Cerebrospinal Fluid Lactate Concentrations in Patients with Bipolar Disorder and Schizophrenia: Implications for the Mitochondrial Dysfunction Hypothesis. Biol. Psychiatry 2009, 65, 489–494. [Google Scholar] [CrossRef] [Green Version]
- Hamraz, M.; Abolhassani, R.; Andriamihaja, M.; Ransy, C.; Lenoir, V.; Schwartz, L.; Bouillaud, F. Hypertonic external medium represses cellular respiration and promotes Warburg/Crabtree effect. FASEB J. 2020, 34, 222–236. [Google Scholar] [CrossRef] [Green Version]
- Spilioti, M.; Evangeliou, A.E.; Tramma, D.; Theodoridou, Z.; Metaxas, S.; Michailidi, E.; Bonti, E.; Frysira, H.; Haidopoulou, A.; Asprangathou, D.; et al. Evidence for treatable inborn errors of metabolism cohort of 187 greek patients with autism spectrum (ASD). Front. Hum. Neurosci. 2013, 7. [Google Scholar] [CrossRef] [Green Version]
- Maurer, I.; Zierz, S.; Möller, H.J. Evidence for a mitochondrial oxidative phosphorylation defect in brains from patients with schizophrenia. Schizophr. Res. 2001, 48, 125–136. [Google Scholar] [CrossRef]
- Xu, Z.; Guo, X.; Yang, Y.; Tucker, D.; Lu, Y.; Xin, N.; Zhang, G.; Yang, L.; Li, J.; Du, X.; et al. Low-Level Laser Irradiation Improves Depression-Like Behaviors in Mice. Mol. Neurobiol. 2017, 54, 4551–4559. [Google Scholar] [CrossRef]
- Sinning, A.; Hübner, C.A. Minireview: PH and synaptic transmission. FEBS Lett. 2013, 587, 1923–1928. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Staub, F.; Mackert, B.; Kempski, O.; Peters, J.; Baethmann, A. Swelling and death of neuronal cells by lactic acid. J. Neurol. Sci. 1993, 119, 79–84. [Google Scholar] [CrossRef]
- Herpertz-Dahlmann, B.; Seitz, J.; Baines, J. Food matters: How the microbiome and gut–brain interaction might impact the development and course of anorexia nervosa. Eur. Child Adolesc. Psychiatry 2017, 26, 1031–1041. [Google Scholar] [CrossRef] [Green Version]
- Theoharides, T.C.; Athanassiou, M.; Panagiotidou, S.; Doyle, R. Dysregulated brain immunity and neurotrophin signaling in Rett syndrome and autism spectrum disorders. J. Neuroimmunol. 2015, 279, 33–38. [Google Scholar] [CrossRef]
- Theoharides, T.C.; Kavalioti, M.; Tsilioni, I. Mast cells, stress, fear and autism spectrum disorder. Int. J. Mol. Sci. 2019, 20, 3611. [Google Scholar] [CrossRef] [Green Version]
- Li, X.; Chauhan, A.; Sheikh, A.M.; Patil, S.; Chauhan, V.; Li, X.M.; Ji, L.; Brown, T.; Malik, M. Elevated immune response in the brain of autistic patients. J. Neuroimmunol. 2009, 207, 111–116. [Google Scholar] [CrossRef] [Green Version]
- Freitas, B.C.; Mei, A.; Mendes, A.P.D.; Beltrão-Braga, P.C.B.; Marchetto, M.C. Modeling inflammation in autism spectrum disorders using stem cells. Front. Pediatr. 2018, 6, 394. [Google Scholar] [CrossRef] [PubMed]
- Belmonte, M.K.; Bourgeron, T. Fragile X syndrome and autism at the intersection of genetic and neural networks. Nat. Neurosci. 2006, 9, 1221–1225. [Google Scholar] [CrossRef] [PubMed]
- Kiyota, K.; Yoshiura, K.-i.; Houbara, R.; Miyahara, H.; Korematsu, S.; Ihara, K. Auto-immune disorders in a child with PIK3CD variant and 22q13 deletion. Eur. J. Med. Genet. 2018, 61, 631–633. [Google Scholar] [CrossRef] [PubMed]
- Kumar, H.; Sharma, B. Minocycline ameliorates prenatal valproic acid induced autistic behaviour, biochemistry and blood brain barrier impairments in rats. Brain Res. 2016, 1630, 83–97. [Google Scholar] [CrossRef] [PubMed]
- Saetre, P.; Emilsson, L.; Axelsson, E.; Kreuger, J.; Lindholm, E.; Jazin, E. Inflammation-related genes up-regulated in schizophrenia brains. BMC Psychiatry 2007, 7. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Van Kesteren, C.F.M.G.; Gremmels, H.; De Witte, L.D.; Hol, E.M.; Van Gool, A.R.; Falkai, P.G.; Kahn, R.S.; Sommer, I.E.C. Immune involvement in the pathogenesis of schizophrenia: A meta-analysis on postmortem brain studies. Transl. Psychiatry 2017, 7, e1075. [Google Scholar] [CrossRef]
- Giridharan, V.V.; Sayana, P.; Pinjari, O.F.; Ahmad, N.; da Rosa, M.I.; Quevedo, J.; Barichello, T. Postmortem evidence of brain inflammatory markers in bipolar disorder: A systematic review. Mol. Psychiatry 2020, 25, 94–113. [Google Scholar] [CrossRef]
- Dantzer, R.; O’Connor, J.C.; Freund, G.G.; Johnson, R.W.; Kelley, K.W. From inflammation to sickness and depression: When the immune system subjugates the brain. Nat. Rev. Neurosci. 2008, 9, 46–56. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Platt, N.; Speak, A.O.; Colaco, A.; Gray, J.; Smith, D.A.; Williams, I.M.; Wallom, K.L.; Platt, F.M. Immune dysfunction in Niemann-Pick disease type C. J. Neurochem. 2016, 136, 74–80. [Google Scholar] [CrossRef] [PubMed]
- Haznedar, M. Volumetric Analysis and Three-Dimensional Glucose Metabolic Mapping of the Striatum and Thalamus in Patients With Autism Spectrum Disorders. Am. J. Psychiatry 2006, 163, 1252. [Google Scholar] [CrossRef]
- Zimmerman, A.W.; Jyonouchi, H.; Comi, A.M.; Connors, S.L.; Milstien, S.; Varsou, A.; Heyes, M.P. Cerebrospinal fluid and serum markers of inflammation in autism. Pediatr. Neurol. 2005, 33, 195–201. [Google Scholar] [CrossRef]
- Vallée, A.; Vallée, J.N. Warburg effect hypothesis in autism Spectrum disorders. Mol. Brain 2018, 11, 1–7. [Google Scholar] [CrossRef] [Green Version]
- Looney, J.M.; Childs, H.M. The lactic acid and glutathione content of the blood of schizophrenic patients. J. Clin. Investig. 1934, 13, 963–968. [Google Scholar] [CrossRef] [Green Version]
- Nau, R.; Brück, W. Neuronal injury in bacterial meningitis: Mechanisms and implications for therapy. Trends Neurosci. 2002, 25, 38–45. [Google Scholar] [CrossRef]
- Myhill, S. Diagnosis and Treatment of Chronic Fatigue Syndrome and Myalgic Encephalitis: It’s Mitochondria, Not Hypochondria; Chelsea Green Publishing: White River Junction, VT, USA, 2018. [Google Scholar]
- Paulson, O.B.; Brodersen, P.; Hansen, E.L.; Kristensen, H.S. Regional cerebral blood flow, cerebral metabolic rate of oxygen, and cerebrospinal fluid acid-base variables in patients with acute meningitis and with acute encephalitis. Acta Med. Scand. 1974, 196, 191–198. [Google Scholar] [CrossRef]
- Kösel, S.; Hofhaus, G.; Maassen, A.; Vieregge, P.; Graeber, M.B. Role of mitochondria in Parkinson disease. Biol. Chem. 1999, 380, 865–870. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Yamamoto, M.; Ujike, H.; Wada, K.; Tsuji, T. Cerebrospinal fluid lactate and pyruvate concentrations in patients with Parkinson’s disease and mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS). J. Neurol. Neurosurg. Psychiatry 1997, 62. [Google Scholar] [CrossRef] [Green Version]
- Quintanilla, R.A.; Jin, Y.N.; Von Bernhardi, R.; Johnson, G.V. Mitochondrial permeability transition pore induces mitochondria injury in Huntington disease. Mol. Neurodegener. 2013, 8, 1–19. [Google Scholar] [CrossRef] [Green Version]
- Koroshetz, W.J.; Jenkins, B.G.; Rosen, B.R.; Flint Beal, M. Energy metabolism defects in Huntington’s disease and effects of coenzyme Q10. Ann. Neurol. 1997, 41, 160–165. [Google Scholar] [CrossRef]
- Calva, E.; Mújica, A.; Núñez, R.; Aoki, K.; Bisteni, A.; Sodi-Pallares, D. Mitochondrial biochemical changes and glucose-KCl-insulin solution in cardiac infarct. Am. J. Physiol. 1966, 211, 71–76. [Google Scholar] [CrossRef]
- Henning, R.J.; Weil, M.H.; Weiner, F. Blood lactate as a prognostic indicator of survival in patients with acute myocardial infarction. Circ. Shock 1982, 9, 307–315. [Google Scholar]
- Marin-Garcia, J.; Goldenthal, M.J.; Moe, G.W. Mitochondrial pathology in cardiac failure. Cardiovasc. Res. 2001, 49, 17–26. [Google Scholar] [CrossRef] [Green Version]
- Sims, N.R.; Muyderman, H. Mitochondria, oxidative metabolism and cell death in stroke. Biochim. Biophys. Acta-Mol. Basis Dis. 2010, 1802, 80–91. [Google Scholar] [CrossRef] [Green Version]
- Bruhn, H.; Frahm, J.; Gyngell, M.L.; Merboldt, K.D.; Hänicke, W.; Sauter, R. Cerebral metabolism in man after acute stroke: New observations using localized proton NMR spectroscopy. Magn. Reson. Med. 1989, 9, 126–131. [Google Scholar] [CrossRef] [Green Version]
- Yamada, H.; Chounan, R.; Higashi, Y.; Kurihara, N.; Kido, H. Mitochondrial targeting sequence of the influenza A virus PB1-F2 protein and its function in mitochondria. FEBS Lett. 2004, 578, 331–336. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Yu, G.; Tzouvelekis, A.; Wang, R.; Herazo-Maya, J.D.; Ibarra, G.H.; Srivastava, A.; De Castro, J.P.W.; Deiuliis, G.; Ahangari, F.; Woolard, T.; et al. Thyroid hormone inhibits lung fibrosis in mice by improving epithelial mitochondrial function. Nat. Med. 2018, 24, 39–49. [Google Scholar] [CrossRef]
- Maher, T.M. Aerobic glycolysis and the warburg effect an unexplored realm in the search for fibrosis therapies? Am. J. Respir. Crit. Care Med. 2015, 192, 1407–1409. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Li, F.; Xu, M.; Wang, M.; Wang, L.; Wang, H.; Zhang, H.; Chen, Y.; Gong, J.; Zhang, J.; Adcock, I.M.; et al. Roles of mitochondrial ROS and NLRP3 inflammasome in multiple ozone-induced lung inflammation and emphysema. Respir. Res. 2018, 19, 230. [Google Scholar] [CrossRef] [PubMed]
- Morrison, W.L.; Gibson, J.N.A.; Scrimgeour, C.; Rennie, M.J. Muscle wasting in emphysema. Clin. Sci. 1988, 75, 415–420. [Google Scholar] [CrossRef]
- Mitsunaga, S.; Hosomichi, K.; Okudaira, Y.; Nakaoka, H.; Suzuki, Y.; Kuwana, M.; Sato, S.; Kaneko, Y.; Homma, Y.; Oka, A.; et al. Aggregation of rare/low-frequency variants of the mitochondria respiratory chain-related proteins in rheumatoid arthritis patients. J. Hum. Genet. 2015, 60, 449–454. [Google Scholar] [CrossRef]
- Oldfors, A.; Moslemi, A.R.; Fyhr, I.M.; Holme, E.; Larsson, N.G.; Lindberg, C. Mitochondrial DNA deletions in muscle fibers in inclusion body myositis. J. Neuropathol. Exp. Neurol. 1995, 54, 581–587. [Google Scholar] [CrossRef]
- Gane, E.J.; Weilert, F.; Orr, D.W.; Keogh, G.F.; Gibson, M.; Lockhart, M.M.; Frampton, C.M.; Taylor, K.M.; Smith, R.A.J.; Murphy, M.P. The mitochondria-targeted anti-oxidant mitoquinone decreases liver damage in a phase II study of hepatitis C patients. Liver Int. 2010, 30, 1019–1026. [Google Scholar] [CrossRef]
- Krähenbühl, S.; Stucki, J.; Reichen, J. Reduced activity of the electron transport chain in liver mitochondria isolated from rats with secondary biliary cirrhosis. Hepatology 1992, 15, 1160–1166. [Google Scholar] [CrossRef]
- Kershenobich, D.; García-Tsao, G.; Saldana, S.A.; Rojkind, M. Relationship between blood lactic acid and serum proline in alcoholic liver cirrhosis. Gastroenterology 1981, 80, 1012–1015. [Google Scholar] [CrossRef]
- Sifroni, K.G.; Damiani, C.R.; Stoffel, C.; Cardoso, M.R.; Ferreira, G.K.; Jeremias, I.C.; Rezin, G.T.; Scaini, G.; Schuck, P.F.; Dal-Pizzol, F.; et al. Mitochondrial respiratory chain in the colonic mucosal of patients with ulcerative colitis. Mol. Cell. Biochem. 2010, 342, 111–115. [Google Scholar] [CrossRef] [PubMed]
- Vernia, P.; Caprilli, R.; Latella, G.; Barbetti, F.; Magliocca, F.M.; Cittadini, M. Fecal Lactate and Ulcerative Colitis. Gastroenterology 1988, 95, 1564–1568. [Google Scholar] [CrossRef]
- Liu, K.M.; Chuang, S.M.; Long, C.Y.; Lee, Y.L.; Wang, C.C.; Lu, M.C.; Lin, R.J.; Lu, J.H.; Jang, M.Y.; Wu, W.J.; et al. Ketamine-induced ulcerative cystitis and bladder apoptosis involve oxidative stress mediated by mitochondria and the endoplasmic reticulum. Am. J. Physiol.-Ren. Physiol. 2015, 309, 318–331. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Brook, I.; Belman, A.B.; Controni, G. Lactic acid in urine of children with lower and upper urinary tract infection and renal obstruction. Am. J. Clin. Pathol. 1981, 75, 110–113. [Google Scholar] [CrossRef] [Green Version]
- Reimer, G. Autoantibodies against nuclear, nucleolar, and mitochondrial antigens in systemic sclerosis (scleroderma). Rheum. Dis. Clin. North Am. 1990, 16, 169–183. [Google Scholar]
- Yang, S.-K.; Zhang, H.-R.; Shi, S.-P.; Zhu, Y.-Q.; Song, N.; Dai, Q.; Zhang, W.; Gui, M.; Zhang, H. The Role of Mitochondria in Systemic Lupus Erythematosus: A Glimpse of Various Pathogenetic Mechanisms. Curr. Med. Chem. 2018, 27, 3346–3361. [Google Scholar] [CrossRef]
- McCaffrey, L.M.; Petelin, A.; Cunha, B.A. Systemic lupus erythematosus (SLE) cerebritis versus Listeria monocytogenes meningoencephalitis in a patient with systemic lupus erythematosus on chronic corticosteroid therapy: The diagnostic importance of cerebrospinal fluid (CSF) of lactic acid levels. Hear. Lung J. Acute Crit. Care 2012, 41, 394–397. [Google Scholar] [CrossRef]
- Daniil, Z.; Kotsiou, O.S.; Grammatikopoulos, A.; Peletidou, S.; Gkika, H.; Malli, F.; Antoniou, K.; Vasarmidi, E.; Mamuris, Z.; Gourgoulianis, K.; et al. Detection of mitochondrial transfer RNA (mt-tRNA) gene mutations in patients with idiopathic pulmonary fibrosis and sarcoidosis. Mitochondrion 2018, 43, 43–52. [Google Scholar] [CrossRef]
- Talreja, J.; Talwar, H.; Bauerfeld, C.; Grossman, L.I.; Zhang, K.; Tranchida, P.; Samavati, L. Hif-1α regulates il-1βand il-17 in sarcoidosis. Elife 2019, 8. [Google Scholar] [CrossRef]
- Busciglio, J.; Pelsman, A.; Wong, C.; Pigino, G.; Yuan, M.; Mori, H.; Yankner, B.A. Altered metabolism of the amyloid β precursor protein is associated with mitochondrial dysfunction in Down’s syndrome. Neuron 2002, 33, 677–688. [Google Scholar] [CrossRef] [Green Version]
- Gross, T.J.; Doran, E.; Cheema, A.K.; Head, E.; Lott, I.T.; Mapstone, M. Plasma metabolites related to cellular energy metabolism are altered in adults with Down syndrome and Alzheimer’s disease. Dev. Neurobiol. 2019, 79, 622–638. [Google Scholar] [CrossRef]
- Shapiro, B.L. Evidence for a mitochondrial lesion in cystic fibrosis. Life Sci. 1989, 44, 1327–1334. [Google Scholar] [CrossRef]
- Emrich, H.M.; Stoll, E.; Friolet, B.; Colombo, J.P.; Richterich, R.; Rossi, E. Sweat composition in relation to rate of sweating in patients with cystic fibrosis of the pancreas. Pediatr. Res. 1968, 2, 464–478. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Abolhassani, M.; Wertz, X.; Pooya, M.; Chaumet-Riffaud, P.; Guais, A.; Schwartz, L. Hyperosmolarity causes inflammation through the methylation of protein phosphatase 2A. Inflamm. Res. 2008, 57, 419–429. [Google Scholar] [CrossRef]
- Schwartz, L.; Israël, M.; Philippe, I. Inflammation and carcinogenesis: A change in the metabolic process. In Cancer Microenvironment and Therapeutic Implications; Baronzio, G., Fiorentini, G., Cogle, C.R., Eds.; Springer: Dordrecht, The Netherlands, 2009; pp. 3–18. ISBN 978-1-4020-9575-7. [Google Scholar]
- Schwartz, L.; Guais, A.; Pooya, M.; Abolhassani, M. Is inflammation a consequence of extracellular hyperosmolarity? J. Inflamm. (Lond.) 2009, 6, 21. [Google Scholar] [CrossRef] [Green Version]
- Németh, Z.H.; Deitch, E.A.; Szabó, C.; Haskó, G. Hyperosmotic stress induces nuclear factor-κB activation and interleukin-8 production in human intestinal epithelial cells. Am. J. Pathol. 2002, 161, 987–996. [Google Scholar] [CrossRef]
- Chassaing, B.; Aitken, J.D.; Malleshappa, M.; Vijay-Kumar, M. Dextran sulfate sodium (DSS)-induced colitis in mice. Curr. Protoc. Immunol. 2014, 104. [Google Scholar] [CrossRef]
- Guo, H.X.; Ye, N.; Yan, P.; Qiu, M.Y.; Zhang, J.; Shen, Z.G.; He, H.Y.; Tian, Z.Q.; Li, H.L.; Li, J.T. Sodium chloride exacerbates dextran sulfate sodium-induced colitis by tuning proinflammatory and antiinflammatory lamina propria mononuclear cells through p38/MAPK pathway in mice. World J. Gastroenterol. 2018, 24, 1779–1794. [Google Scholar] [CrossRef]
- Schwartz, L.; Abolhassani, M.; Pooya, M.; Steyaert, J.-M.; Wertz, X.; Israël, M.; Guais, A.; Chaumet-Riffaud, P. Hyperosmotic stress contributes to mouse colonic inflammation through the methylation of protein phosphatase 2A. Am. J. Physiol. Gastrointest. Liver Physiol. 2008, 295, G934–G941. [Google Scholar] [CrossRef] [Green Version]
- Chan, P.H.; Wong, Y.P.; Fishman, R.A. Hyperosmolality-induced GABA release from rat brain slices: Studies of calcium dependency and sources of release. J. Neurochem. 1978, 30, 1363–1368. [Google Scholar] [CrossRef]
- Marchi, N.; Tierney, W.; Alexopoulos, A.V.; Puvenna, V.; Granata, T.; Janigro, D. The Etiological Role of Blood-Brain Barrier Dysfunction in Seizure Disorders. Cardiovasc. Psychiatry Neurol. 2011. [Google Scholar] [CrossRef] [Green Version]
- Rosen, A.S.; Andrew, R.D. Osmotic effects upon excitability in rat neocortical slices. Neuroscience 1990, 38, 579–590. [Google Scholar] [CrossRef]
- Chan, P.H.; Pollack, E.; Fishman, R.A. Differential effects of hypertonic mannitol and glycerol on rat brain metabolism and amino acids. Brain Res. 1981, 225, 143–153. [Google Scholar] [CrossRef]
- Radman, M. Cellular parabiosis and the latency of age-related diseases. Open Biol. 2019, 9, 180250. [Google Scholar] [CrossRef] [Green Version]
- Alfarouk, K.O.; Verduzco, D.; Rauch, C.; Muddathir, A.K.; Bashir, A.H.H.; Elhassan, G.O.; Ibrahim, M.E.; Orozco, P.J.D.; Cardone, R.A.; Reshkin, S.J.; et al. Glycolysis, tumor metabolism, cancer growth and dissemination. A new pH-based etiopathogenic perspective and therapeutic approach to an old cancer question. Oncoscience 2014, 1, 777–802. [Google Scholar] [CrossRef]
- Ortega, A.D.; Sánchez-Aragó, M.; Giner-Sánchez, D.; Sánchez-Cenizo, L.; Willers, I.; Cuezva, J.M. Glucose avidity of carcinomas. Cancer Lett. 2009, 276, 125–135. [Google Scholar] [CrossRef]
- Alfarouk, K.O.; Ahmed, S.B.M.; Ahmed, A.; Elliott, R.L.; Ibrahim, M.E.; Ali, H.S.; Wales, C.C.; Nourwali, I.; Aljarbou, A.N.; Bashir, A.H.H.; et al. The interplay of dysregulated ph and electrolyte imbalance in cancer. Cancers 2020, 12, 898. [Google Scholar] [CrossRef] [Green Version]
- Alfarouk, K.O.; Muddathir, A.K.; Shayoub, M.E.A. Tumor acidity as evolutionary spite. Cancers 2011, 3, 408. [Google Scholar] [CrossRef] [Green Version]
- Schwartz, L.; Seyfried, T.; Alfarouk, K.O.; Da Veiga Moreira, J.; Fais, S. Out of Warburg effect: An effective cancer treatment targeting the tumor specific metabolism and dysregulated pH. Semin. Cancer Biol. 2017, 43, 134–138. [Google Scholar] [CrossRef]
- Schwartz, L.; Supuran, C.T.; Alfarouk, K.O. The Warburg effect and the Hallmarks of Cancer. Anticancer. Agents Med. Chem. 2017, 17, 164–170. [Google Scholar] [CrossRef]
- Gatenby, R.A.; Gillies, R.J. A microenvironmental model of carcinogenesis. Nat. Rev. Cancer 2008, 8, 56–61. [Google Scholar] [CrossRef]
- Webb, B.A.; Chimenti, M.; Jacobson, M.P.; Barber, D.L. Dysregulated pH: A perfect storm for cancer progression. Nat. Rev. Cancer 2011, 11, 671–677. [Google Scholar] [CrossRef]
- Lee, C.H.; Cragoe, E.J.; Edwards, A.M. Control of hepatocyte DNA synthesis by intracellular pH and its role in the action of tumor promoters. J. Cell. Physiol. 2003, 195, 61–69. [Google Scholar] [CrossRef]
- Karagiannis, J.; Young, P.G. Intracellular pH homeostasis during cell-cycle progression and growth state transition in Schizosaccharomyces pombe. J. Cell Sci. 2001, 114, 2929–2941. [Google Scholar]
- Alfarouk, K.O.; Stock, C.-M.; Taylor, S.; Walsh, M.; Muddathir, A.K.; Verduzco, D.; Bashir, A.H.H.; Mohammed, O.Y.; Elhassan, G.O.; Harguindey, S.; et al. Resistance to cancer chemotherapy: Failure in drug response from ADME to P-gp. Cancer Cell Int. 2015, 15, 71. [Google Scholar] [CrossRef] [Green Version]
- Alfarouk, K.O. Tumor metabolism, cancer cell transporters, and microenvironmental resistance. J. Enzym. Inhib. Med. Chem. 2016, 6366, 1–8. [Google Scholar] [CrossRef] [Green Version]
Entropy Released as Biomass | Entropy Released as Heat |
---|---|
Anabolism | Catabolism |
Lactic Fermentation | Respiration |
Anaerobic Glycolysis | Oxidative Phosphorylation |
Proliferation | Cell Differentiation |
Reduction | Oxidation |
Low ATP synthesis | High ATP synthesis |
Low water activity | High water activity |
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Schwartz, L.; Henry, M.; Alfarouk, K.O.; Reshkin, S.J.; Radman, M. Metabolic Shifts as the Hallmark of Most Common Diseases: The Quest for the Underlying Unity. Int. J. Mol. Sci. 2021, 22, 3972. https://doi.org/10.3390/ijms22083972
Schwartz L, Henry M, Alfarouk KO, Reshkin SJ, Radman M. Metabolic Shifts as the Hallmark of Most Common Diseases: The Quest for the Underlying Unity. International Journal of Molecular Sciences. 2021; 22(8):3972. https://doi.org/10.3390/ijms22083972
Chicago/Turabian StyleSchwartz, Laurent, Marc Henry, Khalid O. Alfarouk, Stephan J. Reshkin, and Miroslav Radman. 2021. "Metabolic Shifts as the Hallmark of Most Common Diseases: The Quest for the Underlying Unity" International Journal of Molecular Sciences 22, no. 8: 3972. https://doi.org/10.3390/ijms22083972