Mitochondria, Metabolism and Disease

Paulo Oliveira

PhD, Principal Investigator

Mitochondria are critical organelles for cell physiology and survival. Mitochondria are the cell energy powerplants, producing most of the chemical energy for cell metabolism, and playing an important role in cell death and quality control processes. Since mitochondria are active players in cellular redox and calcium homeostasis, as well as in intermediate metabolism, our general objective is to provide insights into the role of mitochondria in cellular metabolism, redox signaling and stress responses associated with chemical toxicology, cancer, cardiovascular and hepatic diseases, osteoporosis, aging-related diseases, and stem cell differentiation. Another objective of our group is to develop interventions to specifically target mitochondria in the context of drug discovery.

The group has distinct objectives in four research lines:

  • Mitochondrial Therapeutics: Development of novel interventions for pharmacological, or non-pharmacological (exercise or diet) regulation of mitochondrial biogenesis/metabolism, and cell quality control in disease; develop high-throughput methods to investigate mitochondrial function in the context of drug discovery.
  • Mitochondria in Toxicology and Disease: Assess mitochondrial dysfunction caused by different xenobiotics, including drugs and nanoparticles; evaluate mechanisms of mitohormesis-mediated cell protection; investigate metabolic and mitochondrial role in the origin and progression of neurodegenerative, cardiometabolic and hepatic diseases.
  • Mitochondrial Physiology in Cancer: Assess the phenotype, metabolic, and mitochondrial remodeling during cancer stem cell differentiation and carcinogenesis; investigate the interactions between the extracellular matrix (ECM), stromal and tumor cells.
  • Osteoporosis and Menopause: Characterize hormone regulation of mitochondrial and metabolic profile of the bone cell; identify phytoestrogens with low toxicological effects and high therapeutic potential for menopausal-associated symptoms.

Group Members

Group Members

Paulo Oliveira (PhD, Group Leader), Manuela Grazina (PhD), Maria João Santos (Superior lab technician, PhD student), Marta Simões (Superior lab technician, PhD student), Célia Gomes (PhD student), Márcia Teixeira (Research grant), Sara Martins (Research grant), Juliana Esgueirão (MSc student), Ana Francisca Ramos (Master in medicine student), Luísa Diogo (MD, PhD), Teresa Lapa (MD, PhD), Armando Carvalho (MD, PhD), Jorge Leitão (MD, PhD), Maria do Carmo Macário (MD, PhD student), João Pedro Marques (MD, PhD student), Pedro Fonseca (MD, PhD student), Paula Garcia (MD), José Bernardes-Correia (MD), Ana Valentim (MD, MSc), João Curto (MD), Ana Duarte (PhD), Carla Lopes (PhD), Cláudia Deus (PhD), Elisabete Ferreiro (PhD), Helena Carvalheiro (PhD), José Teixeira (PhD), Sandra Mota (PhD), Susana Pereira (PhD), Teresa Cunha-Oliveira (PhD), Adriana Carvalho (PhD student), Ana Pedrosa (PhD student), Caroline Veloso (PhD student), Débora Mena (PhD student), Gabriela Oliveira (PhD student), Gonçalo Afonso (PhD student), Luís Grilo (PhD student), Margarida Sobral (PhD student), Pedro Valente (PhD student), Ricardo Amorim (PhD student), Sónia Pinho (PhD student), Carolina Tocantins (MSc student), Catarina Mendes (MSc student), Henrique Tavares (MSc student), José Pedro Baptista (MSc student), Mariana Diniz (MSc student), Rafael Silveira (MSc student), Daniel Silva (Gestor de projetos), Catarina Melim (Técnica de laboratório), Pedro Monteiro (MD, PhD), Carlos M. Palmeira (PhD), Anabela P. Rolo (PhD), João Soeiro (PhD), Ivo Machado (PhD student), Rui Silva (PhD student), Carolina Santos Pinto (MSc student), Carmen Alpoim (PhD), Manuela Ferreira (PhD), Patrícia Bastos Amador (PhD), Júlio Torres (MSc student), Soraia Faria (MSc student), Guilherme Silvério (Bsc student).

Selected Publications

Sex-dependent vulnerability of fetal nonhuman primate cardiac mitochondria to moderate maternal nutrient reduction Susana P. Pereira; Ludgero C. Tavares; Ana I. Duarte; Inês Baldeiras; Teresa Cunha-Oliveira; João D. Martins; Maria S. Santos; et al, Clinical Science. 1103 - 1126. 9. 135. 2021. https://doi.org/10.1042/CS20201339

Mitochondrial and metabolic remodeling in human skin fibroblasts in response to glucose availability Pinho, Sónia A.; Costa, Cláudio F.; Deus, Cláudia M.; Pinho, Sonia L.C.; Miranda-Santos, Inês; Afonso, Gonçalo; Bagshaw, Olivia; et al, The FEBS Journal. 2022. http://dx.doi.org/10.1111/febs.16413

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, Redox Biology. 2021. https://dx.doi.org/10.1016/j.redox.2021.102037

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, Free Radical Biology and Medicine. 119 - 132. 179. 2022. http://dx.doi.org/10.1016/j.freeradbiomed.2021.12.304

Bajzikova, M., Kovarova, J., Coelho, A. R., Boukalova, S., Oh, S., Rohlenova, K., Svec, D., Hubackova, S., Endaya, B., Judasova, K., et al. (2019). Reactivation of Dihydroorotate Dehydrogenase-Driven Pyrimidine Biosynthesis Restores Tumor Growth of Respiration-Deficient Cancer Cells. Cell Metab 29(2), 399-416 e10.

Magalhaes-Novais, S., Bermejo-Millo, J. C., Loureiro, R., Mesquita, K. A., Domingues, M. R., Maciel, E., Melo, T., Baldeiras, I., Erickson, J. R., Holy, J., et al. (2019). Cell quality control mechanisms maintain stemness and differentiation potential of P19 embryonic carcinoma cells. Autophagy doi: 10.1080/15548627.2019.1607694, 1-21.

Bacalhau, M., Simões, M., Rocha, M. C., Hardy, S. A., Vincent, A. E., Durães, J., ... & Grazina, M. (2018). Disclosing the functional changes of two genetic alterations in a patient with Chronic Progressive External Ophthalmoplegia: Report of the novel mtDNA m. 7486G> A variant. Neuromuscular Disorders, 28(4), 350-360.

Mitochondrial and metabolic dysfunction in ageing and age-related diseases. Amorim JA, Coppotelli G, Rolo AP, Palmeira CM, Ross JM, Sinclair DA. Nat Rev Endocrinol. 2022 Feb 10. doi: 10.1038/s41574-021-00626-7.

The Soluble Adenylyl Cyclase Inhibitor LRE1 Prevents Hepatic Ischemia/Reperfusion Damage Through Improvement of Mitochondrial Function. Teodoro JS, Amorim JA, Machado IF, Castela AC, Steegborn C, Sinclair DA, Rolo AP, Palmeira CM. Int J Mol Sci. 2020 Jul 11;21(14):4896. doi: 10.3390/ijms21144896.

Strategies for Cancer Immunotherapy Using Induced Pluripotency Stem Cells-Based Vaccines. De Jesus BB ; Neves BM; Ferreira M; Nóbrega-Pereira S. Cancers 12 12 (2020): 3581-3581. https://doi.org/10.3390/cancers12123581.

Selected Grants

“FOIE GRAS”, H2020-MSCA-ITN-2016, Proposal 722619, 2017-2020 (European Commission)

“mtFOIE GRAS”, H2020-MSCA-RISE-2016, Proposal 734719, 2017-2020 (European Commission)

"Human Neuronal Cells Differentiated from Urine-derived Stem Cells as a Platform for Personalized Medicine in Amyotrophic Lateral Sclerosis" PTDC/BTM-ORG/0055/2021; Universidade de Coimbra Centro de Neurociências e Biologia Celular. Funders: Fundação para a Ciência e a Tecnologia

"Development and validation of innovative screening methods for mitochondrial health modulators" PTDC/BTM-SAL/29297/2017; Universidade de Coimbra Centro de Neurociências e Biologia Celular; Universidade de Coimbra; Funders: Fundação para a Ciência e a Tecnologia

"Mit.OnOff : Malfunctions of the energy factory / Avarias na fábrica de energia" fbr_oc2_01_universidade de coimbra; Universidade de Coimbra; Universitetet i Bergen; Funders: EEA Grants Portugal

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