Clin. Bioenerg., Volume 1, Issue 1 (September 2025) – 7 articles

Vanadium is a transition metal whose environmental presence has increased due to human activities such as fossil fuel combustion and industrial processes. A central mechanism of its toxicity involves mitochondrial dysfunction, as vanadium exposure disrupts energy metabolism, enhances reactive oxygen species (ROS) generation, and triggers oxidative stress, ultimately leading to genetic damage and alterations in cellular signaling. These mitochondrial alterations contribute to its potential carcinogenic, immunotoxic, and neurotoxic properties, affecting multiple systems, including the neurological, renal, immune, and reproductive systems. Since there are no specific treatments for vanadium intoxication, natural compounds—particularly plant-derived metabolites with antioxidant, mitochondrial-targeted, and chelating properties—have been investigated as potential therapeutic agents to counteract its toxicity. In this context, simple models such as the nematode Caenorhabditis elegans (C. elegans), the fruit fly (Drosophila melanogaster), and the zebrafish (Danio rerio) have emerged as valuable experimental systems for studying vanadium-induced mitochondrial dysfunction and evaluating protective strategies. These organisms offer key advantages, including a short life cycle, ease of handling, and conservation of essential biological pathways with mammals, making them effective tools in environmental toxicology. The aim of this review is to outline the mitochondrial-related toxic effects of vanadium across different biological models and to explore plant-based therapeutic approaches capable of mitigating its harmful health impacts. We also propose the use of simple models, such as D. melanogaster, D. rerio, and, most notably, C. elegans, as versatile and complementary experimental platforms to advance research in this field. Full article

Psychiatric disorders such as major depressive disorder, bipolar disorder, and schizophrenia are now recognized as complex systemic conditions in which mitochondrial dysfunction and oxidative stress are key contributors to their pathophysiology. Mitochondria, beyond their role in ATP synthesis, are critical for calcium regulation, immune responses, and apoptosis, and their impairment affects brain function. This review examines current evidence from transcriptomics, metabolomics, neuroimaging, and preclinical studies, which consistently show disruptions in oxidative phosphorylation, mitochondrial fragmentation, altered mitochondrial DNA, and heightened inflammatory activity across these disorders. We integrate recent advances with the understanding of mitochondrial bioenergetics in the brain, the contribution of redox imbalance to neural dysfunction, the crosstalk between mitochondria and immune mechanisms, and the relevance of these processes to clinical symptoms. Furthermore, we highlight the promise of bioenergetic biomarkers and emerging interventions targeting mitochondrial pathways, including antioxidants, AMPK-SIRT1-PGC-1α axis modulators, physical exercise, and mitoprotective agents. Peripheral metabolic signatures and neuroimaging modalities are also discussed as tools for diagnostic refinement and individualized therapeutic approaches. These insights underscore the centrality of mitochondrial health in psychiatric disease and support the development of precision psychiatry grounded in metabolic phenotyping. Full article

Tumor cells often exhibit mitochondrial dysfunction and a pronounced glycolytic shift (the “Warburg effect”) that alters the tumor microenvironment. These metabolic changes, including mitochondrial DNA mutations and impaired oxidative phosphorylation, confer survival advantages and can reduce sensitivity to chemotherapeutics such as paclitaxel. In hypoxic environments, cancer cells upregulate glycolysis via HIF-1α, consequently lowering the extracellular pH through lactate secretion, which is associated with resistance to paclitaxel. Likewise, cancer-associated fibroblasts and immune cells undergo metabolic reprogramming in the tumor microenvironment. Glycolytic CAFs produce lactate and pyruvate that fuel tumor cells, reinforcing drug resistance, and tumor-driven polarization of macrophages toward an immunosuppressive M2 phenotype further impairs the anti-tumor response. Here, we review recent findings on how these metabolic adaptations attenuate paclitaxel efficacy and discuss strategies to overcome resistance. We highlight 15 key studies that reported cancer types, metabolic alterations, molecular targets, and outcomes related to paclitaxel response. Overall, the data suggest that targeting metabolic vulnerabilities, for example, by inhibiting glycolysis (HK2, PGAM1, and PDK) or modulating mitochondrial function, may restore paclitaxel sensitivity. Understanding metabolic crosstalk in the tumor microenvironment provides a basis for combined therapies that improve outcomes in paclitaxel-resistant cancers. Full article

Mitochondrial integrity is indispensable for pulmonary cellular homeostasis, with its dysfunction increasingly being implicated as a central mechanism in the etiology of respiratory disorders. We present a comprehensive overview of the integral role played by mitochondrial dynamics, such as fusion, fission, mitophagy, intracellular trafficking, and biogenesis, in maintaining pulmonary homeostasis. This study further explores how perturbations in these processes contribute to the pathogenesis of diverse lung disorders, including chronic obstructive pulmonary disease (COPD), bronchopulmonary dysplasia (BPD), pulmonary arterial hypertension (PAH), idiopathic pulmonary fibrosis (IPF), and drug-induced lung disease. It further explores how perturbations in these processes contribute to the pathogenesis of diverse lung disorders—for example, chronic obstructive pulmonary disease (COPD; responsible for roughly 55% of chronic respiratory disease cases), bronchopulmonary dysplasia (BPD; affecting up to 45% of infants born before 29 weeks of gestation), pulmonary arterial hypertension (PAH; a rare condition causing about 22,000 deaths worldwide in 2021), idiopathic pulmonary fibrosis (IPF; 0.33–4.51 cases per 10,000 persons), and drug-induced lung disease. Evidence demonstrates that mitochondria-triggered apoptosis, metabolic shifts, and subsequent inflammatory signaling act together to drive airway tissue remodeling and fibrotic progression across these lung diseases. Furthermore, this review evaluates the therapeutic potential of mitochondrial-targeted drugs, such as MitoQ and SS31, and metformin, which have shown promise in basic and preclinical studies. Preclinical and early clinical evaluations include an ongoing trial of the mitochondrial-targeted antioxidant MitoQ (NCT02966665, phase 1) in COPD, a 4-month open-label DCA study in PAH patients, and studies determining the preclinical efficacy of SS-31 and metformin in IPF models. Ultimately, integrating mitochondrial biomarkers into clinical practice holds the potential not only to facilitate early disease detection but also to enable the development of precision therapies, thereby offering renewed hope for patients afflicted with chronic lung diseases. Full article

Background/Objectives: Traumatic brain injury (TBI) affects millions of people worldwide, with approximately 2.8 million cases occurring in the United States each year. These injuries may be mild, moderate, or severe based on intensity of impact. The damage caused by TBI results not only from the initial injury, but also from secondary damage due to oxidative stress. Oxidative stress is the increase in reactive oxygen and nitrogen species and the decrease in overall antioxidant capacity, which can lead to a loss of protein function. There is currently no treatment for TBI, only alleviation of symptoms. Glutathione, the most potent antioxidant in the brain, is capable of reducing oxidative damage. Methods: This study investigates the efficacy of gamma-glutamylcysteine ethyl ester (GCEE), a glutathione analog, as a post-therapeutic treatment option in moderate TBI using enzymatic analysis. Enzymatic analysis indicates that key metabolic enzymes of TBI samples treated with GCEE significantly increase in activity relative to traumatically brain injured rats treated with a saline treatment. Protein and gene expression of TBI samples treated with GCEE was also analyzed and compared to that of control and saline-treated samples. Results: Glutathione-related enzymes were found to be increased in GCEE-treated animals compared to saline, thereby showing an increase in antioxidant defense from gamma-glutamylcysteine ethyl ester. Conclusions: Results demonstrate GCEE as a promising post-therapeutic treatment for moderate TBI. Full article

The literature on creatine biomarkers in various bodily fluids remains limited. The purpose of this review is to explore the available data regarding the presence of molecules considered biomarkers of creatine metabolism—namely creatine, guanidinoacetate, and creatinine—across different bodily fluids and matrices. In addition to providing reference values for each biofluid, the paper reports concentrations of these biomarkers in different pathologies. The impairment of creatine metabolism is most extensively studied in creatine deficiency syndromes, which are characterized by genetic deficiencies in either the enzymes involved in creatine biosynthesis or creatine transport. However, other conditions may also influence creatine metabolism to some extent. Our paper also focuses on the transport pathways of these metabolites from their originating tissues to various bodily fluids, typically mediated by the creatine transporter (SLC6A8), with evidence suggesting the involvement of other transporters as well. Gas and liquid chromatography have replaced traditional methods for the analytical detection of biomarkers of creatine metabolism and are now commonly used for this purpose. The paper also discusses the differences and variations between these analytical methods. Full article