Amitriptyline, a tricyclic antidepressant, has been proposed as an antitumoral drug in oxidative therapy. Its pro-apoptotic effects, mediated by high reactive oxygen species generation, have been already described. In this study we analysed the effect of amitriptyline on the biosynthesis of coenzyme Q (CoQ), an essential component for electron transport and a potent membrane antioxidant involved in redox signaling. We treated H460 cells, a non-small-cell lung cancer cell line, with amitriptyline and we analysed CoQ levels by HPLC and CoQ biosynthesis rate, as well as the enzymes involved in CoQ biosynthesis by real-time PCR and Western blot. Amitriptyline treatment induced a dose-dependent decrease in CoQ levels in tumor cells. CoQ decreased levels were associated with down-regulation of the expression of COQ4 gene, as well as decreased Coq4 and Coq6 protein levels. Our findings suggest that the effect of amitriptyline on CoQ biosynthesis highlights the potential of this drug for antitumoral oxidative therapy.
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http://dx.doi.org/10.1016/j.ejphar.2017.01.017 | DOI Listing |
Int J Mol Sci
December 2024
Faculty of Medicine, Slovak Medical University, Limbová 12, 833 03 Bratislava, Slovakia.
Fertility disorders are a worldwide problem affecting 8-12% of the population, with the male factor substantially contributing to about 40-50% of all infertility cases. Mitochondria, crucial organelles for cellular viability, play a pivotal role in the processes of spermatogenesis and significantly affect sperm quality and their fertilizing ability. Mitochondrial oxidative phosphorylation (OXPHOS) dysfunction, reduced energy supply for sperm, reduced endogenous coenzyme Q (CoQ) levels, and oxidative stress are among the main factors that contribute to male infertility.
View Article and Find Full Text PDFJ Neurochem
January 2025
The Laboratory of Molecular Gerontology, National Institute on Aging, National Institutes of Health, Bethesda, Maryland, USA.
Alzheimer disease is a neurodegenerative pathology-modifying mitochondrial metabolism with energy impairments where the effects of biological sex and DNA repair deficiencies are unclear. We investigated the therapeutic potential of dietary ketosis alone or with supplemental nicotinamide riboside (NR) on hippocampal intermediary metabolism and mitochondrial bioenergetics in older male and female wild-type (Wt) and 3xTgAD-DNA polymerase-β-deficient (3xTg/POLβ) (AD) mice. DNA polymerase-β is a key enzyme in DNA base excision repair (BER) of oxidative damage that may also contribute to mitochondrial DNA repair.
View Article and Find Full Text PDFFree Radic Biol Med
January 2025
Department of Neurology, Columbia University Medical Center, New York, NY, 10032, USA. Electronic address:
Coenzyme Q (CoQ) is a critical component of the mitochondrial respiratory chain. CoQ deficiencies often cause a variety of clinical syndromes, often involving encephalopathies. The heterogeneity of clinical manifestations implies different pathomechanisms, reflecting CoQ involvement in several biological processes.
View Article and Find Full Text PDFWater Res
December 2024
College of Water Sciences, Beijing Normal University, Beijing 100875, China; Beijing ENFI Environmental Protection Co., Ltd., Beijing, 100038, China.
The impact of nanominerals on microbial electron transfer and energy metabolism strategies during pollutant degradation remains uncertain. This study used in situ synthesized FeS nanoparticles (FeS NPs) to increase the degradation efficiency of SMX by anaerobic bacterial communities from 25.80 % to 47.
View Article and Find Full Text PDFPhysiol Rev
December 2024
Institute of Metabolism and Cell Death, Molecular Targets and Therapeutics Center, Helmholtz Zentrum München, Ingolstädter Landstr. 1, 85764 Neuherberg, Germany.
We present here a comprehensive update on recent advancements in the field of ferroptosis, with a particular emphasis on its metabolic underpinnings and physiological impacts. After briefly introducing landmark studies that have helped to shape the concept of ferroptosis as a distinct form of cell death, we critically evaluate the key metabolic determinants involved in its regulation. These include the metabolism of essential trace elements such as selenium and iron; amino acids such as cyst(e)ine, methionine, glutamine/glutamate and tryptophan; and carbohydrates, covering glycolysis, the citric acid cycle, the electron transport chain and the pentose phosphate pathway.
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