Can the Pareto optimality theory reveal cellular trade-offs in diffuse large B-Cell lymphoma transcriptomic data? DOI Creative Commons
Jonatan Blais, Julie Jeukens

Research Square (Research Square), Год журнала: 2023, Номер unknown

Опубликована: Окт. 20, 2023

Abstract One of the main challenges in cancer treatment is selection resistant clones which leads to emergence resistance previously efficacious therapies. Identifying vulnerabilities form cellular trade-offs constraining phenotypic possibility space could allow avoid by simultaneously targeting processes that are involved different alternative strategies linked trade-offs. The Pareto optimality theory has been proposed as a framework allowing identify such biological data from its prediction it would lead presence specific geometrical patterns (polytopes) e.g. gene expression space, with vertices representing specialized phenotypes. We tested this approach diffuse large B-cell lymphoma (DLCBL) transcriptomic data. As predicted, there was highly statistically significant evidence for forming tetrahedron defining four phenotypes (archetypes). These archetypes were significantly enriched certain functions, and contained genes formed pattern shared unique elements among archetypes, expected if between essential functions underlie observed structure. results can be interpreted reflecting aerobic energy production protein synthesis, immunotolerant immune escape strategies. Targeting on both sides these represent potential promising avenues therapeutic applications.

Язык: Английский

Potential of Copper and Copper Compounds for Anticancer Applications DOI Creative Commons
Peng Ji, Peng Wang, Hao Chen

и другие.

Pharmaceuticals, Год журнала: 2023, Номер 16(2), С. 234 - 234

Опубликована: Фев. 3, 2023

Inducing cancer cell death has always been a research hotspot in life sciences. With the continuous deepening and diversification of related research, potential value metal elements inducing explored. Taking iron as an example, ferroptosis, mainly characterized by increasing load driving production large amounts lipid peroxides eventually leading to death, recently attracted great interest community. After iron, copper, trace element, received extensive attention especially tumor death. Copper its complexes can induce autophagy or apoptosis cells through variety different mechanisms action (activation stress pathways, arrest cycle, inhibition angiogenesis, cuproptosis, paraptosis), which are promising therapy have become new hotspots treatment research. This article reviews main applications novel copper compound-induced focusing on compounds their anticancer applications.

Язык: Английский

Процитировано

85
Mitochondria Need Their Sleep: Redox, Bioenergetics, and Temperature Regulation of Circadian Rhythms and the Role of Cysteine-Mediated Redox Signaling, Uncoupling Proteins, and Substrate Cycles DOI Creative Commons
Richard B. Richardson, Ryan J. Mailloux

Antioxidants, Год журнала: 2023, Номер 12(3), С. 674 - 674

Опубликована: Март 9, 2023

Although circadian biorhythms of mitochondria and cells are highly conserved crucial for the well-being complex animals, there is a paucity studies on reciprocal interactions between oxidative stress, redox modifications, metabolism, thermoregulation, other major oscillatory physiological processes. To address this limitation, we hypothesize that circadian/ultradian interaction redoxome, bioenergetics, temperature signaling strongly determine differential activities sleep-wake cycling mammalians birds. Posttranslational modifications proteins by reversible cysteine oxoforms, S-glutathionylation S-nitrosylation shown to play role in regulating mitochondrial reactive oxygen species production, protein activity, respiration, metabolomics. Nuclear DNA repair cellular synthesis maximized during wake phase, whereas redoxome restored remodeling sleep. Hence, our analysis reveals wakefulness more protective restorative nucleus (nucleorestorative), sleep (mitorestorative). The "redox-bioenergetics-temperature mitochondrial-nuclear regulatory hypothesis" adds understanding respiratory uncoupling, substrate control hibernation. Similarly, hypothesis explains how redox-bioenergetics-temperature-regulated states, when perturbed interactome disturbances, influence pathogenesis aging, cancer, spaceflight health effects, sudden infant death syndrome, diseases metabolism nervous system.

Язык: Английский

Процитировано

23
Extracellular vesicles meet mitochondria: Potential roles in regenerative medicine DOI Creative Commons

Shujie Wu,

Tao Yang,

Meirui Ma

и другие.

Pharmacological Research, Год журнала: 2024, Номер 206, С. 107307 - 107307

Опубликована: Июль 14, 2024

Extracellular vesicles (EVs), secreted by most cells, act as natural cell-derived carriers for delivering proteins, nucleic acids, and organelles between cells. Mitochondria are highly dynamic responsible energy production cellular physiological processes. Recent evidence has highlighted the pivotal role of EVs in intercellular mitochondrial content transfer, including DNA (mtDNA), intact mitochondria. Intriguingly, mitochondria crucial mediators release, suggesting an interplay their potential implications physiology pathology. However, this expanding field, much remains unknown regarding function mechanism crosstalk transport EVs. Herein, we shed light on pathological functions mitochondria, mechanisms underlying interactions, delivery mitochondria-rich EVs, clinical applications regenerative medicine.

Язык: Английский

Процитировано

10
The Balance of MFN2 and OPA1 in Mitochondrial Dynamics, Cellular Homeostasis, and Disease DOI Creative Commons
Paola Zanfardino, Alessandro Amati,

M Perrone

и другие.

Biomolecules, Год журнала: 2025, Номер 15(3), С. 433 - 433

Опубликована: Март 18, 2025

Mitochondrial dynamics, governed by fusion and fission, are crucial for maintaining cellular homeostasis, energy production, stress adaptation. MFN2 OPA1, key regulators of mitochondrial fusion, play essential roles beyond their structural functions, influencing bioenergetics, intracellular signaling, quality control mechanisms such as mitophagy. Disruptions in these processes, often caused or OPA1 mutations, linked to neurodegenerative diseases like Charcot-Marie-Tooth disease type 2A (CMT2A) autosomal dominant optic atrophy (ADOA). This review explores the molecular underlying impact dysfunction on oxidative phosphorylation autophagy, role progression. Additionally, we discuss divergent responses particularly terms proliferation, senescence, metabolic signaling. Finally, highlight emerging therapeutic strategies restore integrity, including mTOR modulation autophagy-targeted approaches, with potential implications disorders.

Язык: Английский

Процитировано

1
MYC—an emerging player in mitochondrial diseases DOI Creative Commons
Janne Purhonen, Juha Klefström, Jukka Kallijärvi

и другие.

Frontiers in Cell and Developmental Biology, Год журнала: 2023, Номер 11

Опубликована: Сен. 4, 2023

The mitochondrion is a major hub of cellular metabolism and involved directly or indirectly in almost all biological processes the cell. In mitochondrial diseases, compromised respiratory electron transfer oxidative phosphorylation (OXPHOS) lead to compensatory rewiring with resemblance Warburg-like metabolic state cancer cells. transcription factor MYC (or c-MYC) regulator cancer, stimulating glycolysis, nucleotide biosynthesis, glutamine utilization, which are known predicted be affected also diseases. Albeit not widely acknowledged thus far, several cell mouse models disease show upregulation and/or its typical transcriptional signatures. Moreover, gene expression metabolite-level changes associated integrated stress response (mt-ISR) remarkable overlap those overexpression. addition being regulator, promotes proliferation modifies cycle kinetics and, especially at high levels, replication genomic instability, sensitizes cells apoptosis. Because requires energy doubling biomass, replicating should particularly sensitive defective OXPHOS. On other hand, OXPHOS-defective vulnerable levels as it facilitates evasion checkpoints accelerates progression. Indeed, few recent studies demonstrate defects nuclear DNA damage OXPHOS deficiency. Here, we give an overview key mitochondria-dependent pathways regulated by MYC, review current literature on speculate how may triggered deficiency what implications this has for pathogenesis these

Язык: Английский

Процитировано

15
Mitochondrial quality control pathways sense mitochondrial protein import DOI
Laurie Lee-Glover, Timothy E. Shutt

Trends in Endocrinology and Metabolism, Год журнала: 2023, Номер 35(4), С. 308 - 320

Опубликована: Дек. 15, 2023

Язык: Английский

Процитировано

11
Pharmacological landscape of endoplasmic reticulum stress: uncovering therapeutic avenues for metabolic diseases DOI
Ghallab Alotaibi,

Abdullah Alkhammash

European Journal of Pharmacology, Год журнала: 2025, Номер unknown, С. 177509 - 177509

Опубликована: Март 1, 2025

Язык: Английский

Процитировано

0
Atovaquone-induced activation of the PERK/eIF2α signaling axis mitigates metabolic radiosensitisation DOI Creative Commons
Jie Feng, Varun Pathak, Niall M. Byrne

и другие.

Cell Communication and Signaling, Год журнала: 2025, Номер 23(1)

Опубликована: Апрель 2, 2025

Язык: Английский

Процитировано

0
The current findings on the gut-liver axis and the molecular basis of NAFLD/NASH associated with gut microbiome dysbiosis DOI
Seema Sharma, Nidhi Tiwari,

Sampat Singh Tanwar

и другие.

Naunyn-Schmiedeberg s Archives of Pharmacology, Год журнала: 2025, Номер unknown

Опубликована: Апрель 9, 2025

Язык: Английский

Процитировано

0
Doxycycline induces mitochondrial dysfunction in aortic smooth muscle cells DOI Creative Commons
Carmen Yap, Shaynah Wanga, Rob C. I. Wüst

и другие.

Vascular Pharmacology, Год журнала: 2024, Номер 154, С. 107279 - 107279

Опубликована: Янв. 23, 2024

The antibiotic doxycycline is known to inhibit inflammation and was therefore considered as a therapeutic prevent abdominal aortic aneurysm (AAA) growth. Yet mitochondrial dysfunction key-characteristic of clinical AAA disease. We hypothesize that impairs function in the aorta smooth muscle cells (SMCs). Doxycycline induced mitonuclear imbalance, reduced proliferation diminished expression typical contractile cell (SMC) proteins. To understand underlying mechanism, we studied krüppel-like factor 4 (KLF4). this transcription enhanced SMCs after treatment. Knockdown KLF4, however, did not affect doxycycline-induced SMC phenotypic changes. Then used bioenergetics drug elamipretide (SS-31). Doxycycline-induced loss contractility markers rescued, but genes connectivity improved upon elamipretide. Thus while anti-inflammatory, it also induces causes switching, potentially contributing pathology. helps mitigate harmful effects on SMC, may be interest for treatment diseases with pre-existing dysfunction.

Язык: Английский

Процитировано

3