Mitochondria‐Nuclear Crosstalk: Orchestrating mtDNA Maintenance DOI Creative Commons
Ghazal Darfarin,

Janice M. Pluth

Environmental and Molecular Mutagenesis, Год журнала: 2025, Номер unknown

Опубликована: Май 26, 2025

ABSTRACT The mitochondria (mt) and nucleus engage in a dynamic bidirectional communication to maintain cellular homeostasis, regulating energy production, stress response, cell fate. Anterograde signaling directs mt function, while retrograde conveys metabolic stress‐related changes from the nucleus. Central this crosstalk is mitochondrial DNA (mtDNA), which encodes key oxidative phosphorylation components. MtDNA integrity preserved through quality control mechanisms, including fusion fission dynamics, mitophagy, nuclear‐encoded repair. Disruption these pathways contributes dysfunction, stress, genetic instability—hallmarks of aging diseases. Additionally, redox NAD+ homeostasis integrate nuclear responses, modulating transcriptional programs that support biogenesis adaptation. This review explores molecular mechanisms coordinating mito‐nuclear interactions, emphasizing their role maintaining mtDNA equilibrium. Understanding processes provides insights into how dysfunction drives disease, paving way for targeted therapeutic strategies.

Язык: Английский

Role of Oxidative Balance Score in Staging and Mortality Risk of Cardiovascular-Kidney-Metabolic Syndrome: Insights from Traditional and Machine Learning Approaches DOI Creative Commons
Yang Chen, Shuang Wu, Hongyu Liu

и другие.

Redox Biology, Год журнала: 2025, Номер 81, С. 103588 - 103588

Опубликована: Март 7, 2025

To evaluate the roles of oxidative balance score (OBS) in staging and mortality risk cardiovascular-kidney-metabolic syndrome (CKM). Data this study were from National Health Nutrition Examination Survey 1999-2018. We performed cross-sectional analyses using multinomial logistic regression to investigate relationship between OBS CKM staging. Cox proportional hazards models used assess impact on outcomes patients. Additionally, mediation explore whether mediated relationships specific predictors (Life's Simple 7 [LS7], systemic immune-inflammation index [SII], frailty score) outcomes. Then, machine learning developed classify stages 3/4 predict all-cause mortality, with SHapley Additive exPlanations values interpret contribution components. 21,609 participants included (20,319 CKM, median [IQR] age: 52.0 [38.0-65.0] years, 54.3% male, follow-up: 9.4 [5.3-14.1] years). Lower quartiles associated advanced Moreover, lower related increased risk, compared Q4 (all-cause mortality: Q1: HR 1.31, 95% CI 1.18-1.46, Q2: 1.27, 1.14-1.42, Q3: 1.18, 1.06-1.32; cardiovascular 1.44, 1.16-1.79, 1.39, 1.11-1.74, 1.26, 1.01-1.57; non-cardiovascular 1.12-1.44, 1.23, 1.08-1.40, 1.16, 1.02-1.31), optimal stratification threshold for was 22. (ranging 4.25%-32.85 %) effects SII, LS7, scores light gradient boosting achieved highest performance predicting (area under curve: 0.905) 0.875). Cotinine while magnesium, vitamin B6, physical activity protective. This highlights as a tool emphasizing stress's role management.

Язык: Английский

Процитировано

3
Synergistic effects of lead and copper co-exposure on promoting oxidative stress and apoptosis in the neuronal cells DOI
Di Wu, Desheng Wang,

Shuang-Shuang Tan

и другие.

Toxicology, Год журнала: 2025, Номер unknown, С. 154103 - 154103

Опубликована: Фев. 1, 2025

Язык: Английский

Процитировано

0
More comprehensive relationship between eGDR and sarcopenia in China: a nationwide cohort study with national representation DOI Creative Commons

Zikai Jin,

Liming Zheng, Chuanrui Sun

и другие.

Diabetology & Metabolic Syndrome, Год журнала: 2025, Номер 17(1)

Опубликована: Март 24, 2025

Although studies had shown that Insulin resistance (IR) was correlated with the occurrence of sarcopenia, there were still many controversial conclusions. Therefore, we conducted a more comprehensive study on relationship between estimated glucose disposal rate (eGDR), an alternative indicator IR, and risk muscle mass, strength to clarify their interactions. The Study included individuals from China Health Retirement Longitudinal (CHARLS) who complete eGDR data at baseline did not develop low mass strength. divided into four subgroups based quartile (Q) eGDR. lowest (Q1) used as reference. Logistic regression linear evaluate sarcopenia (low strength, possible sarcopenia) related features (ASM/Ht2, grip, RMS), respectively. In addition, further evaluated nonlinear using smooth curve fitting threshold effect analysis. results showed after adjusting for confounders, negatively associated positively characteristics. men significant reduction in likelihood compared women. But levels rise, women gain ASM/Ht2. Further analysis revealed inverse correlation ASM/Ht2 inflection point 15.3893. Besides that, grip (7.1862) RMS (11.1042) before point. found higher lower developing sarcopenia. However, effects need be considered comprehensively. For it is recommended maintain below 15.3893, 7.1862, potential benefits early warning

Язык: Английский

Процитировано

0
Activation of SIK1 by phanginin A regulates skeletal muscle glucose uptake by phosphorylating HADC4/5/7 and enhancing GLUT4 expression and translocation DOI Creative Commons
Yu Shi,

Xing‐De Wu,

Yanli Liu

и другие.

Natural Products and Bioprospecting, Год журнала: 2025, Номер 15(1)

Опубликована: Апрель 7, 2025

Abstract Salt-inducible kinase 1 (SIK1) participates in various physiological processes, yet its involvement regulating skeletal muscle glucose uptake remains unclear. Previously, we showed that phanginin A, a natural compound isolated from Caesalpinia sappan Linn , activated SIK1 to suppress gluconeogenesis hepatocytes. Here, aimed elucidate the effects of on by using A. The C2C12 myotubes were incubated with A and then uptake, mRNA levels, membrane GLUT4 content, phosphorylation levels proteins SIK1/HDACs Akt/AS160 signaling pathways determined. Phanginin significantly promoted while pan-SIK inhibitor or knocking down expression abolished promotion. Further exploration enhanced increasing histone deacetylase (HDAC) 4/5 MEF2a protein level, blocked these effects. Additionally, induced HDAC7 phosphorylation, upregulated junction plakoglobin (JUP) phosphorylation. Knocking JUP both attenuated A-induced suggesting activation inactivated increase led upregulation translocation uptake. In vivo study increased SIK1, HDAC4/5/7, Akt/AS160, gene MEF2a, JUP, accompanied elevated glycogen content gastrocnemius C57BL/6 J mice, indicating utilization. These findings reveal novel mechanism stimulates through phosphorylating HADC4/5/7 subsequent enhancement translocation. Graphical abstract

Язык: Английский

Процитировано

0
Transcriptomic analysis of muscle and adipose tissues identifies myokines and adipokines contributing to lipid deposition in Taoyuan Black pigs DOI Creative Commons
Liu Guo, Jianzhong Xu,

Wenyue Zhou

и другие.

Animal nutrition, Год журнала: 2025, Номер unknown

Опубликована: Апрель 1, 2025

Язык: Английский

Процитировано

0
Integrated Metabolomics and Lipidomics Analysis Reveals the Mechanism Behind the Action of Chiglitazar on the Protection Against Sepsis-Induced Acute Lung Injury DOI Creative Commons

Liu-Liu Lu,

Yubin Cao,

Zhen-Chen Lu

и другие.

Metabolites, Год журнала: 2025, Номер 15(5), С. 290 - 290

Опубликована: Апрель 25, 2025

Background: Sepsis-induced acute lung injury (SALI) is a critical clinical challenge with high mortality. Metabolic dysregulation drives SALI pathogenesis, disrupting function and energy metabolism. Despite proven benefits, metabolic restoration underused in sepsis. This study explores chiglitazar's role balancing metabolism to protect against SALI. Methods: The protective effects of chiglitazar CLP rats were demonstrated by the survival curve, histological analysis, immunohistochemical analysis tissue. Metabolomic lipidomic analyses tissue samples using gas chromatography-mass spectrometry (GC-MS) liquid (LC-MS) performed evaluate shifts induced surgery pretreatment. mRNA protein levels underlying targets directing nicotinamide adenine dinucleotide (NAD+) triglyceride synthesis analyzed qPCR Western blotting. To validate mechanism which protected SALI, SIRT1 inhibitor EX-527 was applied human normal epithelial (BEAS-2B) cells another batch observe its reverse effect action. Results: Chiglitazar pretreatment significantly restored NAD+ improved dysregulated lipid enhancing triglycerides (TGs) suppressing accumulated fatty acids (FAs). modulation mediated associated upregulations SIRT1/PGC-1α/PPARα/GPAT3 axis. Co-treatment LPS-stimulated BEAS-2B inhibited on aforementioned signaling pathways worsened injury, respectively. Conclusions: alleviates restoring TG synthesis, highlighting as promising therapeutic strategy management

Язык: Английский

Процитировано

0
The Ferroptosis–Mitochondrial Axis in Depression: Unraveling the Feedforward Loop of Oxidative Stress, Metabolic Homeostasis Dysregulation, and Neuroinflammation DOI Creative Commons

Xu Liu,

Qiang Luo,

Yulong Zhao

и другие.

Antioxidants, Год журнала: 2025, Номер 14(5), С. 613 - 613

Опубликована: Май 20, 2025

Emerging evidence links ferroptosis–mitochondrial dysregulation to depression pathogenesis through an oxidative stress–energy deficit–neuroinflammation cycle driven by iron overload. This study demonstrates that accumulation initiates ferroptosis via Fenton reaction-mediated lipid peroxidation, compromising neuronal membrane integrity and disabling the GPx4 antioxidant system. Concurrent mitochondrial complex I/IV dysfunction impairs ATP synthesis, creating AMPK/mTOR signaling imbalance calcium dyshomeostasis synergistically impair synaptic plasticity. Bidirectional crosstalk emerges: peroxidation derivatives oxidize cardiolipin, while ROS overproduction activates ACSL4 amplify ferroptotic susceptibility, forming a self-reinforcing neurodegenerative loop. Prefrontal–hippocampal metabolomics reveal paradoxical metabolic reprogramming with glycolytic compensation suppressing biogenesis (via PGC-1α/TFAM downregulation), trapping neurons in bioenergetic crisis. Clinical data further show microglial M1 polarization cGAS-STING activation sustains neuroinflammation IL-6/TNF-α release. We propose “ferroptosis–mitochondrial fragmentation–metabolic maladaptation” triad as mechanistic subtyping criteria for depression. Preclinical validation shows combinatorial therapy (iron chelators + SIRT3 agonists) rescues viability restoring energy flux. work shifts therapeutic paradigms from monoaminergic targets toward multimodal strategies addressing homeostasis, organelle dynamics, vulnerability—a framework significant implications developing neuroprotective antidepressants.

Язык: Английский

Процитировано

0
Age‐Related Oxidative Stress and Mitochondrial Dysfunction in Lymph Node Stromal Cells Limit the Peripheral T Cell Homeostatic Maintenance and Function DOI Creative Commons
Sandip Ashok Sonar, Ruchika Bhat, H. Lorraine Thompson

и другие.

Aging Cell, Год журнала: 2025, Номер unknown

Опубликована: Май 21, 2025

ABSTRACT Lymph nodes (LN) are the key organs in charge of long‐term maintenance naïve lymphocytes and their initial, primary activation upon infection. Accumulating evidence indicates that LN stromal cells undergo degenerative changes with aging critically impair function, including generation protective immune responses. The nature these defects remains incompletely understood. We here demonstrate age‐related manifest themselves mitochondrial dysfunction oxidative stress. Ex vivo, all three major cell subsets, fibroblastic reticular (FRC), lymphatic endothelial (LEC), blood (BEC) exhibit elevated reactive oxygen species (ROS) stress, reduced potential, mass aging. Old FRC also exhibited cytoplasmic ROS production. This was accompanied by ability old to support Tn survival vitro, a defect alleviated pretreating stroma general antioxidant N ‐acetyl cysteine (NAC) as well ROS‐reducing (mitoquinone) mitophagy‐inducing (urolithin A) compounds. Mitochondrial and, particular, potential were seen vaccination or infection vivo. Consistent results, vivo treatment mice NAC restored adult levels numbers antigen‐specific CD8 + effector T production granzyme B response antigenic challenge.

Язык: Английский

Процитировано

0
Mitochondria‐Nuclear Crosstalk: Orchestrating mtDNA Maintenance DOI Creative Commons
Ghazal Darfarin,

Janice M. Pluth

Environmental and Molecular Mutagenesis, Год журнала: 2025, Номер unknown

Опубликована: Май 26, 2025

ABSTRACT The mitochondria (mt) and nucleus engage in a dynamic bidirectional communication to maintain cellular homeostasis, regulating energy production, stress response, cell fate. Anterograde signaling directs mt function, while retrograde conveys metabolic stress‐related changes from the nucleus. Central this crosstalk is mitochondrial DNA (mtDNA), which encodes key oxidative phosphorylation components. MtDNA integrity preserved through quality control mechanisms, including fusion fission dynamics, mitophagy, nuclear‐encoded repair. Disruption these pathways contributes dysfunction, stress, genetic instability—hallmarks of aging diseases. Additionally, redox NAD+ homeostasis integrate nuclear responses, modulating transcriptional programs that support biogenesis adaptation. This review explores molecular mechanisms coordinating mito‐nuclear interactions, emphasizing their role maintaining mtDNA equilibrium. Understanding processes provides insights into how dysfunction drives disease, paving way for targeted therapeutic strategies.

Язык: Английский

Процитировано

0