Metabolism, Aging and Disease

MitoPerOx Mitochondrial-Peroxisome Metabolic and Redox Crosstalk

Mitochondria

Peroxisome

Lipid Metabolism

ROS metabolism

Mitochondrial Medicine


Research lines

• Molecular elucidation of mitochondria-peroxisome crosstalk in health and disease • Impact of mitochondrial redox imbalance in the transformation of peroxisomal function and vice-versa in disease pathology • Pharmacological interventions to improve disease phenotype through restoration of mitochondrial function

Overview

Mitochondrial and peroxisomal function is strongly interconnected as they exhibit complementary activities, share proteins and communicate with each other. Metabolically, both organelles are jointly involved to degrade fatty acids and contribute to the detoxification of reactive oxygen species generated in cellular processes. Importantly, mitochondrial dysfunction is likely to induce peroxisomal impairment and vice versa, but the precise contribution of each organelle to disease pathology and development is not yet clear and likely to be complex. Our laboratory takes an integrative approach to study mitochondria and peroxisomes biology of in the context of metabolic disorders.
One important aspect of our work is to investigate the role of mitochondria-peroxisomes crosstalk in complex cellular processes (lipid metabolism, ROS metabolism, organelle dynamics and dysfunctions) to provide insight how mitochondria and peroxisomes exchange co-factors, metabolites, and signaling molecules.
A second important aspect is to determine how mitochondrial/peroxisomal ROS contributes to human pathologies and whether cellular redox imbalance of these organelles impact human disorders via cellular studies and mouse models.
Finally, we take this information and use it to rationally design potential therapies for diseases that arise from mitochondria-peroxisome crosstalk imbalance. Our research is also devoted to exploring the medicinal chemistry of natural versatile molecules with promising therapeutic applications, such as phenolic acids and their derivatives. Currently our main focus for therapy is the Non-Alcoholic Fatty Liver Disease (NAFLD).

Publications

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Information about journal articles, updated at 26-06-2022, from platform CIÊNCIAVITAE.

Mitochondriotropic antioxidant based on caffeic acid AntiOxCIN4 activates Nrf2-dependent antioxidant defenses and quality control mechanisms to antagonize oxidative stress-induced cell damage

Amorim, Ricardo; Cagide, Fernando; Tavares, Ludgero C.; Simões, Rui F.; Soares, Pedro; Benfeito, Sofia; Baldeiras, Inês; et al, 2022. Free Radical Biology and Medicine. 119 - 132. 179. 2022. http://dx.doi.org/10.1016/j.freeradbiomed.2021.12.304 . 10.1016/j.freeradbiomed.2021.12.304 . Free Radical Biology and Medicine

Cytoskeleton alterations in non-alcoholic fatty liver disease

Pessoa, João; Teixeira, José, 2022. Metabolism. 128. 2022. http://dx.doi.org/10.1016/j.metabol.2021.155115 . 10.1016/j.metabol.2021.155115 . Metabolism

Cytotoxicity and Mitochondrial Effects of Phenolic and Quinone-Based Mitochondria-Targeted and Untargeted Antioxidants on Human Neuronal and Hepatic Cell Lines: A Comparative Analysis

Fernandes, Carlos; Videira, Afonso J. C.; Veloso, Caroline D.; Benfeito, Sofia; Soares, Pedro; Martins, João D.; Gonçalves, Beatriz; et al, 2021. Biomolecules. 11. 11. 2021. http://dx.doi.org/10.3390/biom11111605 . 10.3390/biom11111605 . Biomolecules

The Alterations of Mitochondrial Function during NAFLD Progression—An Independent Effect of Mitochondrial ROS Production

Simões, Inês C. M.; Amorim, Ricardo; Teixeira, José; Karkucinska-Wieckowska, Agnieszka; Carvalho, Adriana; Pereira, Susana P.; Simões, Rui F.; et al, 2021. International Journal of Molecular Sciences. 13. 22. 2021. http://dx.doi.org/10.3390/ijms22136848 . 10.3390/ijms22136848 . International Journal of Molecular Sciences

A mitochondria-targeted caffeic acid derivative reverts cellular and mitochondrial defects in human skin fibroblasts from male sporadic Parkinson's disease patients

Deus, Cláudia M.; Pereira, Susana P.; Cunha-Oliveira, Teresa; Teixeira, José; Simões, Rui F.; Cagide, Fernando; Benfeito, Sofia; et al, 2021. Redox Biology. 45. 2021. http://dx.doi.org/10.1016/j.redox.2021.102037 . 10.1016/j.redox.2021.102037 . Redox Biology

Exploratory Data Analysis of Cell and Mitochondrial High-Fat, High-Sugar Toxicity on Human HepG2 Cells

Amorim, Ricardo; Simões, Inês C. M.; Veloso, Caroline; Carvalho, Adriana; Simões, Rui F.; Pereira, Francisco B.; Thiel, Theresa; et al, 2021. Nutrients. 5. 13. 2021. http://dx.doi.org/10.3390/nu13051723 . 10.3390/nu13051723 . Nutrients

Mitochondria-targeted phenolic antioxidants induce ROS-protective pathways in primary human skin fibroblasts

Teixeira, José; Basit, Farhan; Willems, Peter H.G.M.; Wagenaars, Jori A.; van de Westerlo, Els; Amorim, Ricardo; Cagide, Fernando; et al, 2021. Free Radical Biology and Medicine. 314 - 324. 163. 2021. http://dx.doi.org/10.1016/j.freeradbiomed.2020.12.023 . 10.1016/j.freeradbiomed.2020.12.023 . Free Radical Biology and Medicine

Transfer of glucose hydrogens via acetyl-CoA, malonyl-CoA, and NADPH to fatty acids during de novo lipogenesis

Belew, Getachew Debas; Silva, Joao; Rito, Joao; Tavares, Ludgero; Viegas, Ivan; Teixeira, Jose; Oliveira, Paulo J.; Macedo, Maria Paula; Jones, John G., 2019. Journal of Lipid Research. 2050 - 2056. 12. 60. 2019. http://dx.doi.org/10.1194/jlr.ra119000354 . 10.1194/jlr.ra119000354 . published Journal of Lipid Research

Benzoic acid-derived nitrones: A new class of potential acetylcholinesterase inhibitors and neuroprotective agents

Oliveira, Catarina; Bagetta, Donatella; Cagide, Fernando; Teixeira, José; Amorim, Ricardo; Silva, Tiago; Garrido, Jorge; et al, 2019. European Journal of Medicinal Chemistry. 116 - 129. 174. 2019. http://dx.doi.org/10.1016/j.ejmech.2019.04.026 . 10.1016/j.ejmech.2019.04.026 . published European Journal of Medicinal Chemistry

Fine-tuning the neuroprotective and blood-brain barrier permeability profile of multi-target agents designed to prevent progressive mitochondrial dysfunction

Benfeito, S.; Oliveira, C.; Fernandes, C.; Cagide, F.; Teixeira, J.; Amorim, R.; Garrido, J.; et al, 2019. European Journal of Medicinal Chemistry. 525 - 545. 167. 2019. http://dx.doi.org/10.1016/j.ejmech.2019.01.055 . 10.1016/j.ejmech.2019.01.055 . published European Journal of Medicinal Chemistry

Discovery of a new mitochondria permeability transition pore (mPTP) inhibitor based on gallic acid

José Teixeira; Catarina Oliveira; Fernando Cagide; Ricardo Amorim; Jorge Garrido; Fernanda Borges; Paulo J. Oliveira, 2018. Journal of Enzyme Inhibition and Medicinal Chemistry. 567 - 576. 1. 33. 2018. https://doi.org/10.1080/14756366.2018.1442831 . 10.1080/14756366.2018.1442831 . published Journal of Enzyme Inhibition and Medicinal Chemistry

Extracellular acidification induces ROS- and mPTP-mediated death in HEK293 cells

Teixeira, J.; Basit, F.; Swarts, H.G.; Forkink, M.; Oliveira, P.J.; Willems, P.H.G.M.; Koopman, W.J.H., 2018. Redox Biology. 394 - 404. 15. 2018. http://www.scopus.com/inward/record.url?eid=2-s2.0-85040366459&partnerID=MN8TOARS . 10.1016/j.redox.2017.12.018 . published Redox Biology

Disruption of mitochondrial function as mechanism for anti-cancer activity of a novel mitochondriotropic menadione derivative

Teixeira, J.; Amorim, R.; Santos, K.; Soares, P.; Datta, S.; Cortopassi, G.A.; Serafim, T.L.; et al, 2018. Toxicology. 123 - 139. 393. 2018. http://www.scopus.com/inward/record.url?eid=2-s2.0-85034013034&partnerID=MN8TOARS . 10.1016/j.tox.2017.11.014 . published Toxicology

Mitochondria: Targeting mitochondrial reactive oxygen species with mitochondriotropic polyphenolic-based antioxidants

Teixeira, José; Deus, Cláudia M.; Borges, Fernanda; Oliveira, Paulo J., 2018. The International Journal of Biochemistry & Cell Biology. 98 - 103. 97. 2018. http://dx.doi.org/10.1016/j.biocel.2018.02.007 . 10.1016/j.biocel.2018.02.007 . published The International Journal of Biochemistry & Cell Biology

Desrisking the Cytotoxicity of a Mitochondriotropic Antioxidant Based on Caffeic Acid by a PEGylated Strategy

Carlos Fernandes; Sofia Benfeito; Ricardo Amorim; José Teixeira; Paulo J. Oliveira; Fernando Remião; Fernanda Borges, 2018. Bioconjugate Chemistry. 2018. https://doi.org/10.1021/acs.bioconjchem.8b00383 . 10.1021/acs.bioconjchem.8b00383 . published Bioconjugate Chemistry

Electrochemical Behavior of a Mitochondria-Targeted Antioxidant at an Interface between Two Immiscible Electrolyte Solutions: An Alternative Approach to Study Lipophilicity

Ribeiro, José A.; Benfeito, Sofia; Cagide, Fernando; Teixeira, José; Oliveira, Paulo J.; Borges, Fernanda; Silva, António F.; Pereira, Carlos M., 2018. Analytical Chemistry. 7989 - 7996. 13. 90. 2018. http://dx.doi.org/10.1021/acs.analchem.8b00787 . 10.1021/acs.analchem.8b00787 . published Analytical Chemistry

Multi-target-directed ligands for Alzheimer's disease: Discovery of chromone-based monoamine oxidase/cholinesterase inhibitors

Reis, Joana; Cagide, Fernando; Valencia, Martín Estrada; Teixeira, José; Bagetta, Donatella; Pérez, Concepción; Uriarte, Eugenio; et al, 2018. European Journal of Medicinal Chemistry. 781 - 800. 158. 2018. http://dx.doi.org/10.1016/j.ejmech.2018.07.056 . 10.1016/j.ejmech.2018.07.056 . published European Journal of Medicinal Chemistry

Sources of hepatic glycogen synthesis in mice fed with glucose or fructose as the sole dietary carbohydrate

Jarak, Ivana; Barosa, Cristina; Martins, Fatima O.; Silva, Joao C. P.; Santos, Cristiano; Belew, Getachew Debas; Rito, Joao; et al, 2018. Magnetic Resonance in Medicine. 639 - 644. 1. 81. 2018. http://dx.doi.org/10.1002/mrm.27378 . 10.1002/mrm.27378 . published Magnetic Resonance in Medicine

Hydroxybenzoic Acid Derivatives as Dual-Target Ligands: Mitochondriotropic Antioxidants and Cholinesterase Inhibitors

Oliveira, Catarina; Cagide, Fernando; Teixeira, José; Amorim, Ricardo; Sequeira, Lisa; Mesiti, Francesco; Silva, Tiago; et al, 2018. Frontiers in Chemistry. 6. 2018. http://dx.doi.org/10.3389/fchem.2018.00126 . 10.3389/fchem.2018.00126 . published Frontiers in Chemistry

Development of a mitochondriotropic antioxidant based on caffeic acid: Proof of concept on cellular and mitochondrial oxidative stress models

Teixeira, J.; Cagide, F.; Benfeito, S.; Soares, P.; Garrido, J.; Baldeiras, I.; Ribeiro, J.A.; et al, 2017. Journal of Medicinal Chemistry. 7084 - 7098. 16. 60. 2017. http://www.scopus.com/inward/record.url?eid=2-s2.0-85028330575&partnerID=MN8TOARS . 10.1021/acs.jmedchem.7b00741 . published Journal of Medicinal Chemistry

Development of hydroxybenzoic-based platforms as a solution to deliver dietary antioxidants to mitochondria

Teixeira, J.; Oliveira, C.; Amorim, R.; Cagide, F.; Garrido, J.; Ribeiro, J.A.; Pereira, C.M.; et al, 2017. Scientific Reports. 1. 7. 2017. http://www.scopus.com/inward/record.url?eid=2-s2.0-85026475854&partnerID=MN8TOARS . 10.1038/s41598-017-07272-y . published Scientific Reports

Dietary Polyphenols and Mitochondrial Function: Role in Health and Disease

Teixeira, J.; Chavarria, D.; Borges, F.; Wojtczak, L.; Wieckowski, M. R.; Karkucinska-Wieckowska, A.; Oliveira, P. J., 2017. Curr Med Chem. 2017. https://www.ncbi.nlm.nih.gov/pubmed/28554320 . 10.2174/0929867324666170529101810 . published Curr Med Chem

Complex I and complex III inhibition specifically increase cytosolic hydrogen peroxide levels without inducing oxidative stress in HEK293 cells

Forkink, M.; Basit, F.; Teixeira, J.; Swarts, H.G.; Koopman, W.J.H.; Willems, P.H.G.M., 2015. Redox Biology. 607 - 616. 6. 2015. http://www.scopus.com/inward/record.url?eid=2-s2.0-84945395305&partnerID=MN8TOARS . 10.1016/j.redox.2015.09.003 . published Redox Biology

Alzheimer's disease, enzyme targets and drug discovery struggles: From natural products to drug prototypes

Silva, T.; Reis, J.; Teixeira, J.; Borges, F., 2014. Ageing Research Reviews. 116 - 145. 1. 15. 2014. http://www.scopus.com/inward/record.url?eid=2-s2.0-84899683262&partnerID=MN8TOARS . 10.1016/j.arr.2014.03.008 . published Ageing Research Reviews

Hydroxycinnamic acid antioxidants: An electrochemical overview

Teixeira, J.; Gaspar, A.; Garrido, E.M.; Garrido, J.; Borges, F., 2013. BioMed Research International. 2013. 2013. http://www.scopus.com/inward/record.url?eid=2-s2.0-84881540701&partnerID=MN8TOARS . 10.1155/2013/251754 . published BioMed Research International

Alzheimer's disease and antioxidant therapy: How long how far?

Teixeira, J.; Silva, T.; Andrade, P.B.; Borges, F., 2013. Current Medicinal Chemistry. 2939 - 2952. 24. 20. 2013. http://www.scopus.com/inward/record.url?eid=2-s2.0-84880283997&partnerID=MN8TOARS . 10.2174/1871523011320240001 . published Current Medicinal Chemistry

Antioxidant therapy: Still in search of the 'magic bullet'

Benfeito, S.; Oliveira, C.; Soares, P.; Fernandes, C.; Silva, T.; Teixeira, J.; Borges, F., 2013. Mitochondrion. 427 - 435. 5. 13. 2013. http://www.scopus.com/inward/record.url?eid=2-s2.0-84882877558&partnerID=MN8TOARS . 10.1016/j.mito.2012.12.002 . published Mitochondrion

Mitochondrial and liver oxidative stress alterations induced by N-butyl-N-(4-hydroxybutyl)nitrosamine: relevance for hepatotoxicity

Oliveira, Maria M.; Teixeira, Jose C.; Vasconcelos-Nobrega, Carmen; Felix, Luis M.; Sardao, Vilma A.; Colaco, Aura A.; Oliveira, Paula A.; Peixoto, Francisco P., 2013. Journal of Applied Toxicology. 434 - 443. 6. 33. 2013. 10.1002/jat.1763 . published Journal of Applied Toxicology

Exploring nature profits: Development of novel and potent lipophilic antioxidants based on galloyl-cinnamic hybrids

Teixeira, J.; Silva, T.; Benfeito, S.; Gaspar, A.; Garrido, E.M.; Garrido, J.; Borges, F., 2013. European Journal of Medicinal Chemistry. 289 - 296. 62. 2013. http://www.scopus.com/inward/record.url?eid=2-s2.0-84873030904&partnerID=MN8TOARS . 10.1016/j.ejmech.2012.12.049 . published European Journal of Medicinal Chemistry

Alzheimer's disease, cholesterol, and statins: The junctions of important metabolic pathways

Silva, T.; Teixeira, J.; Remião, F.; Borges, F., 2013. Angewandte Chemie - International Edition. 1110 - 1121. 4. 52. 2013. http://www.scopus.com/inward/record.url?eid=2-s2.0-84872382364&partnerID=MN8TOARS . 10.1002/anie.201204964 . published Angewandte Chemie - International Edition

Rational discovery and development of a mitochondria-targeted antioxidant based on cinnamic acid scaffold

Teixeira, J.; Soares, P.; Benfeito, S.; Gaspar, A.; Garrido, J.; Murphy, M.P.; Borges, F., 2012. Free Radical Research. 600 - 611. 5. 46. 2012. http://www.scopus.com/inward/record.url?eid=2-s2.0-84859067775&partnerID=MN8TOARS . 10.3109/10715762.2012.662593 . published Free Radical Research

Mg2+-doped poly(epsilon-caprolactone)/siloxane biohybrids

Teixeira, J. C. S.; Fernandes, M.; Bermudez, V. de Zea; Barbosa, P. C.; Rodrigues, L. C.; Silva, M. M.; Smith, M. J., 2010. Electrochimica Acta. 1328 - 1332. 4. 55. 2010. 10.1016/j.electacta.2009.06.024 . published Electrochimica Acta

Awards

2022

Stimulus of Scientific Employment, Individual Support (CEECIND) - 3rd Edition - Foundation for Science and Technology (FCT),

2018

ESCI 2018 Poster Award from ESCI 2018 - European Society for Clinical Investigation, Barcelona

2017

ITC Conference Grant from COST – European Cooperation in Science & Technology – Action CA15135. Vienna

2016

Award of Excellence from Paul Ehrlich MedChem Euro-PhD Network - MuTaLig COST Action CA15135. Budapest

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