Mitochondrial DNA Dynamics in Reprogramming to Pluripotency DOI Creative Commons
Alexander J. Sercel,

Natasha M. Carlson,

Alexander N. Patananan

et al.

Trends in Cell Biology, Journal Year: 2021, Volume and Issue: 31(4), P. 311 - 323

Published: Jan. 9, 2021

Mammalian cells, with the exception of erythrocytes, harbor mitochondria, which are organelles that provide energy, intermediate metabolites, and additional activities to sustain cell viability, replication, function. Mitochondria contain multiple copies a circular genome called mitochondrial DNA (mtDNA), whose individual sequences rarely identical (homoplasmy) because inherited or sporadic mutations result in mtDNA genotypes (heteroplasmy). Here, we examine potential mechanisms for maintenance shifts heteroplasmy occur induced pluripotent stem cells (iPSCs) generated by cellular reprogramming, further discuss manipulations can alter impact differentiated performance. This insight will assist developing more robust iPSC-based models disease therapies.

Language: Английский

Mitochondrial DNA copy number in human disease: the more the better? DOI Creative Commons
Roberta Filograna, Mara Mennuni, David Alsina

et al.

FEBS Letters, Journal Year: 2020, Volume and Issue: 595(8), P. 976 - 1002

Published: Dec. 12, 2020

Most of the genetic information has been lost or transferred to nucleus during evolution mitochondria. Nevertheless, mitochondria have retained their own genome that is essential for oxidative phosphorylation (OXPHOS). In mammals, a gene‐dense circular mitochondrial DNA (mtDNA) about 16.5 kb encodes 13 proteins, which constitute only 1% proteome. Mammalian mtDNA present in thousands copies per cell and mutations often affect fraction them. pathogenic human are recessive cause OXPHOS defects if above certain critical threshold. However, emerging evidence strongly suggests proportion mutated not determinant disease but also absolute copy number matters. this review, we critically discuss current knowledge role regulation various types diseases, including disorders, neurodegenerative disorders cancer, ageing. We provide an overview new exciting therapeutic strategies directly manipulate restore diseases.

Language: Английский

Citations

355
Cancer metabolism and mitochondria: Finding novel mechanisms to fight tumours DOI Creative Commons
Sonia Missiroli, Mariasole Perrone, Ilaria Genovese

et al.

EBioMedicine, Journal Year: 2020, Volume and Issue: 59, P. 102943 - 102943

Published: Aug. 17, 2020

Mitochondria are dynamic organelles that have essential metabolic activity and regarded as signalling hubs with biosynthetic, bioenergetics functions orchestrate key biological pathways. However, mitochondria can influence all processes linked to oncogenesis, starting from malignant transformation metastatic dissemination. In this review, we describe how alterations in the mitochondrial status contribute acquisition of typical traits, discussing most recent discoveries many unanswered questions. We also highlight expanding our understanding regulation function mechanisms context cancer cell metabolism could be an important task biomedical research, thus offering possibility targeting for treatment cancer.

Language: Английский

Citations

188
An Epigenetic Role of Mitochondria in Cancer DOI Creative Commons
Yue Liu, Chao Chen, Xinye Wang

et al.

Cells, Journal Year: 2022, Volume and Issue: 11(16), P. 2518 - 2518

Published: Aug. 13, 2022

Mitochondria are not only the main energy supplier but also cell metabolic center regulating multiple key metaborates that play pivotal roles in epigenetics regulation. These metabolites include acetyl-CoA, α-ketoglutarate (α-KG), S-adenosyl methionine (SAM), NAD+, and O-linked beta-N-acetylglucosamine (O-GlcNAc), which substrates for DNA methylation histone post-translation modifications, essential gene transcriptional regulation fate determination. Tumorigenesis is attributed to many factors, including mutations tumor microenvironment. initiation, evolution, metastasis, recurrence. Targeting mitochondrial metabolism promising therapeutic strategies treatment. In this review, we summarize of mitochondria required modification discuss current strategy cancer therapies via targeting epigenetic modifiers related enzymes This review an important contribution understanding metabolic-epigenetic-tumorigenesis concept.

Language: Английский

Citations

87
Discovery of the Highly Selective and Potent STAT3 Inhibitor for Pancreatic Cancer Treatment DOI Creative Commons
Chen Huang, Aiwu Bian, Wenbo Zhou

et al.

ACS Central Science, Journal Year: 2024, Volume and Issue: 10(3), P. 579 - 594

Published: Feb. 10, 2024

Signal transducer and activator of transcription 3 (STAT3) is an attractive cancer therapeutic target. Unfortunately, targeting STAT3 with small molecules has proven to be very challenging, for full activation STAT3, the cooperative phosphorylation both tyrosine 705 (Tyr705) serine 727 (Ser727) needed. Further, a selective inhibitor dual not been developed. Here, we identified low nanomolar potency highly small-molecule that simultaneously inhibits Tyr705 Ser727 phosphorylation. YY002 potently inhibited STAT3-dependent tumor cell growth in vitro achieved potent suppression metastasis vivo. More importantly, exhibited favorable pharmacokinetics, acceptable safety profile, superior antitumor efficacy compared BBI608 (STAT3 advanced into phase III trials). For mechanism, selectively bound Src Homology 2 (SH2) domain over other STAT members, which strongly suppressed nuclear mitochondrial functions cells. Collectively, this study suggests potential inhibitors as possible anticancer agents.

Language: Английский

Citations

16
The Common Hallmarks of Aging, Circadian Rhythms and Cancer: Implications for Therapeutic Strategies DOI Creative Commons
Jie Wang, Fanglin Shao, Qingxin Yu

et al.

Research, Journal Year: 2025, Volume and Issue: 8

Published: Jan. 1, 2025

The intricate relationship between cancer, circadian rhythms, and aging is increasingly recognized as a critical factor in understanding the mechanisms underlying tumorigenesis cancer progression. Aging well-established primary risk for while disruptions rhythms are intricately associated with progression of various tumors. Moreover, itself disrupts leading to physiological changes that may accelerate development. Despite these connections, specific interplay processes their collective impact on remains inadequately explored literature. In this review, we systematically explore influence We discuss how core genes tumor prognosis, highlighting shared hallmarks such genomic instability, cellular senescence, chronic inflammation. Furthermore, examine aging, focusing crosstalk contributes tumorigenesis, proliferation, apoptosis, well metabolism stability. By elucidating common pathways linking review provides new insights into pathophysiology identifies potential therapeutic strategies. propose targeting regulation could pave way novel treatments, including chronotherapy antiaging interventions, which offer important benefits clinical management cancer.

Language: Английский

Citations

2
Mitochondria in brain diseases: Bridging structural-mechanistic insights into precision-targeted therapies DOI Creative Commons
Jun Liao, Wenxiu He, Lisha Li

et al.

Published: Feb. 1, 2025

Language: Английский

Citations

2
Arginine is an epigenetic regulator targeting TEAD4 to modulate OXPHOS in prostate cancer cells DOI Creative Commons
Chia‐Lin Chen, Sheng-Chieh Hsu,

Tan-Ya Chung

et al.

Nature Communications, Journal Year: 2021, Volume and Issue: 12(1)

Published: April 23, 2021

Arginine plays diverse roles in cellular physiology. As a semi-essential amino acid, arginine deprivation has been used to target cancers with synthesis deficiency. Arginine-deprived cancer cells exhibit mitochondrial dysfunction, transcriptional reprogramming and eventual cell death. In this study, we show prostate that acts as an epigenetic regulator modulate histone acetylation, leading global upregulation of nuclear-encoded oxidative phosphorylation (OXPHOS) genes. TEAD4 is retained the nucleus by arginine, enhancing its recruitment promoter/enhancer regions OXPHOS genes mediating coordinated YAP1-independent but mTOR-dependent manner. also activates expression lysine acetyl-transferases increases overall levels acetylated histones acetyl-CoA, facilitating recruitment. Silencing suppresses functions growth vitro vivo. Given strong correlation carcinogenesis, targeting may be beneficially enhance arginine-deprivation therapy therapy.

Language: Английский

Citations

85
Mitochondrial DNA is a major source of driver mutations in cancer DOI Creative Commons
Min‐Soo Kim, Mahnoor Mahmood, Ed Reznik

et al.

Trends in cancer, Journal Year: 2022, Volume and Issue: 8(12), P. 1046 - 1059

Published: Aug. 27, 2022

Somatic mutations to mitochondrial DNA (mtDNA) in cancers are abundant, but their selection is highly gene and context dependent.Truncating tRNA mtDNA drivers certain diseases, the function of vast majority somatic variants uncharacterized.Heteroplasmic dosage likely a critical determinant phenotype produced by mutations.New techniques for single-cell profiling technologies genome editing overcome key obstacles delineating cancer. Mitochondrial among most common genetic events all tumors directly impact metabolic homeostasis. Despite central role mitochondria play energy metabolism cellular physiology, genomes has been contentious. Until recently, genomic functional studies were impeded lack adequate tumor sequencing data available methods engineering. These barriers conceptual fog surrounding have begun lift, revealing path understanding this essential cancer initiation progression. Here we discuss history, recent developments, challenges that remain oncogenetics as major new class cancer-associated unveiled.

Language: Английский

Citations

53
Mitochondrial and metabolic alterations in cancer cells DOI Creative Commons
Jacopo Di Gregorio, Sabrina Petricca, Roberto Iorio

et al.

European Journal of Cell Biology, Journal Year: 2022, Volume and Issue: 101(3), P. 151225 - 151225

Published: April 13, 2022

Metabolic alterations have been observed in many cancer types. The deregulated metabolism has thus become an emerging hallmark of the disease, where is frequently rewired to aerobic glycolysis. This led concept "metabolic reprogramming", which therefore extensively studied. Over years, it characterized enhancement glycolysis, key mutations some enzymes TCA cycle, and increased glucose uptake, are used by cells achieve a phenotype" useful gain proliferation advantage. Many studies highlighted detail signaling pathways molecular mechanisms responsible for glycolytic switch. However, glycolysis not only metabolic process that rely on. Oxidative Phosphorylation (OXPHOS), gluconeogenesis or beta-oxidation fatty acids (FAO) may be involved development progression several tumors. In cases, these metabolisms even more crucial than tumor survival. review will focus on contribution survival cancers. We also analyze balance between processes regulated, as well therapeutical approaches can derive from their study.

Language: Английский

Citations

45
Metabolic changes during prostate cancer development and progression DOI Creative Commons

Alicia-Marie K. Beier,

Martin Puhr, Matthias B. Stope

et al.

Journal of Cancer Research and Clinical Oncology, Journal Year: 2022, Volume and Issue: 149(5), P. 2259 - 2270

Published: Sept. 23, 2022

Abstract Metabolic reprogramming has been recognised as a hallmark in solid tumours. Malignant modification of the tumour’s bioenergetics provides energy for tumour growth and progression. Otto Warburg first reported these metabolic biochemical changes 1927. In prostate cancer (PCa) epithelial cells, metabolism also during development progress. These alterations are partly driven by androgen receptor, key regulator PCa development, progress, survival. contrast to other cells different entities, glycolytic sustains physiological citrate secretion normal prostatic epithelium. early stages PCa, is utilised power oxidative phosphorylation fuel lipogenesis, enabling advanced incurable castration-resistant shift towards choline, amino acid, fueling progression described. Therefore, even if not fully understood, altered may provide opportunities novel therapeutic strategies, especially stages. This review focuses on main differences PCa’s tumourigenesis highlighting glutamine’s role PCa.

Language: Английский

Citations

38