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Intermediary metabolism: An intricate network at the crossroads of cell fate an...
Leonardo M. R. Ferreira, Leonardo M. R.; Li, Albert M.; Serafim, Teresa L.; Sobral, Margarida C.; Alpoim, Maria Carmen; Urbano, Ana M.Intermediary metabolism is traditionally viewed as the large, highly integrated network of reactions that provides cells with metabolic energy, reducing power and biosynthetic intermediates. The elucidation of its major pathways and molecular mechanisms of energy transduction occupied some of the brightest scientific minds for almost two centuries. When these goals were achieved, a sense that intermediary metab...
Reactivation of Dihydroorotate Dehydrogenase-Driven Pyrimidine Biosynthesis Res...
Bajzikova, Martina; Kovarova, Jaromira; Coelho, Ana R.; Boukalova, Stepana; Oh, Sehyun; Rohlenova, Katerina; Svec, David; Hubackova, SonaCancer cells without mitochondrial DNA (mtDNA) do not form tumors unless they reconstitute oxidative phosphorylation (OXPHOS) by mitochondria acquired from host stroma. To understand why functional respiration is crucial for tumorigenesis, we used time-resolved analysis of tumor formation by mtDNA-depleted cells and genetic manipulations of OXPHOS. We show that pyrimidine biosynthesis dependent on respiration-l...
Metabolic and Phenotypic Characterization of Human Skin Fibroblasts After Forci...
Pereira, Susana P.; Deus, Cláudia M.; Serafim, Teresa L.; Cunha-Oliveira, Teresa; Oliveira, Paulo J.Human skin fibroblasts present technical advantages for the study of mitochondrial-induced toxicity, because those cells can be isolated from patients by lowly invasive methods and present specific cumulative cellular damage and mutations of particular conditions. Several drugs lead to organ toxicity, with some of these drugs having been already withdrawn from the market. Frequently, drug-induced toxicity is at...
Berberine-induced cardioprotection and Sirt3 modulation in doxorubicin-treated ...
Coelho, Ana R.; Martins, Tatiana R.; Couto, Renata; Deus, Cláudia; Pereira, Cláudia V.; Simões, Rui F.; Rizvanov, Albert A.; Silva, FilomenaDoxorubicin (DOX) is one of the most widely used anti-neoplastic agents. However, treatment with DOX is associated with cumulative cardiotoxicity inducing progressive cardiomyocyte death. Sirtuin 3 (Sirt3), a mitochondrial deacetylase, regulates the activity of proteins involved in apoptosis, autophagy and metabolism. Our hypothesis is that pharmacological modulation by berberine (BER) pre-conditioning of Sirt3...
Role of mtDNA-related mitoepigenetic phenomena in cancer
Ferreira, André; Serafim, Teresa L.; Sardão, Vilma A.; Cunha-Oliveira, TeresaAbnormal mitochondrial function has long been associated with the development and the progression of cancer. Multiple defects in the mitochondrial genome have been reported for various cancers, however the often disregarded mitochondrial epigenetic landscape provides an additional source of deregulation that may contribute to carcinogenesis.
Analysis of pro-apoptotic protein trafficking to and from mitochondria
Vega-Naredo, Ignacio; Cunha-Oliveira, Teresa; Serafim, Teresa L.; Sardão, Vilma A.; Oliveira, Paulo J.Mitochondria play a key role in cell death and its regulation. The permeabilization of the outer mitochondrial membrane which is mainly controlled by proteins of the BCL-2 family, is a key event that can be directly induced by p53 and results in the release of pro-apoptotic factors to the cytosol, such as cytochrome c, second mitochondria derived activator of caspases/direct inhibitor-of-apoptosis (IAP) binding...
New derivatives of lupane triterpenoids disturb breast cancer mitochondria and ...
Serafim, Teresa L.; Carvalho, Filipa S.; Bernardo, Telma C.; Pereira, Gonçalo C.; Perkins, Edward; Holy, Jon; Krasutsky, Dmytro A.Novel cationic dimethylaminopyridine derivatives of pentacyclic triterpenes were previously described to promote mitochondrial depolarization and cell death in breast and melanoma cell lines. The objective of this work was to further investigate in detail the mechanism of mitochondrial perturbations, correlating those effects with breast cancer cell responses to those same agents. Initially, a panel of tumor an...
Dimethylaminopyridine derivatives of lupane triterpenoids cause mitochondrial d...
Bernardo, Telma C.; Cunha-Oliveira, Teresa; Serafim, Teresa L.; Holy, Jon; Krasutsky, Dmytro; Kolomitsyna, Oksana; Krasutsky, Pavel; Moreno, A. J. M.Triterpenoids are a large class of naturally occurring compounds, and some potentially interesting as anticancer agents have been found to target mitochondria. The objective of the present work was to investigate the mechanisms of mitochondrial toxicity induced by novel dimethylaminopyridine (DMAP) derivatives of pentacyclic triterpenes, which were previously shown to inhibit the growth of melanoma cells in vit...
Lipophilic Caffeic and Ferulic Acid Derivatives Presenting Cytotoxicity against...
Serafim, Teresa L.; Carvalho, Filipa S.; Marques, Maria P. M.; Calheiros, Rita; Silva, Tiago; Garrido, Jorge; Milhazes, Nuno; Borges, FernandaIn the present work, lipophilic caffeic and ferulic acid derivatives were synthesized, and their cytotoxicity on cultured breast cancer cells was compared. A total of six compounds were initially evaluated: caffeic acid (CA), hexyl caffeate (HC), caffeoylhexylamide (HCA), ferulic acid (FA), hexyl ferulate (HF), and feruloylhexylamide (HFA). Cell proliferation, cell cycle progression, and apoptotic signaling wer...
Lipophilic Caffeic and Ferulic Acid Derivatives Presenting Cytotoxicity against...
Serafim, Teresa L.; Carvalho, Filipa S.; Marques, Maria P. M.; Calheiros, Rita; Silva, Tiago; Garrido, J.M.P.J.; Milhazes, Nuno; Borges, FernandaIn the present work, lipophilic caffeic and ferulic acid derivatives were synthesized, and their cytotoxicity on cultured breast cancer cells was compared. A total of six compounds were initially evaluated: caffeic acid (CA), hexyl caffeate (HC), caffeoylhexylamide (HCA), ferulic acid (FA), hexyl ferulate (HF), and feruloylhexylamide (HFA). Cell proliferation, cell cycle progression, and apoptotic signaling wer...