bims-mistre 2025-03-16 papers

bims-mistre

Biomed News

on Mito stress

Issue of 2025–03–16
twelve papers selected by
Ellen Siobhan Mitchell, MitoQ

Mitochondrial Dysfunction in Cardiovascular Diseases.
Role of Mitochondrial Dynamics in Skin Homeostasis: An Update.
Q-Der: a next-generation CoQ10 analogue supercharging neuroprotection by combating oxidative stress and enhancing mitochondrial function.
Insulin resistance in Alzheimer's disease: signalling mechanisms and therapeutics strategies.
Mitochondria-targeted nanovesicles for ursodeoxycholic acid delivery to combat neurodegeneration by ameliorating mitochondrial dysfunction.
Vascular dysfunction in Alzheimer's disease: Exploring the potential of aerobic and resistance exercises as therapeutic strategies.
5-Methoxytryptophan Attenuates Oxidative Stress-Induced Downregulation of PINK1 and Mitigates Mitochondrial Damage and Apoptosis in Cardiac Myocytes.
The Nuclear-Mitochondrial Crosstalk in Aging: From Mechanisms to Therapeutics.
27-Hydroxymangiferolic Acid Extends Lifespan and Improves Neurodegeneration in Caenorhabditis elegans by Activating Nuclear Receptors.
Iron metabolism and ferroptosis in health and diseases: the crucial role of mitochondria in meta-bolically active tissues.
Reversing Glycation with a Dietary Supplement Containing Rosemary Extract.
GSK3 coordinately regulates mitochondrial activity and nucleotide metabolism in quiescent oocytes.

Int J Mol Sci. 2025 Feb 23. pii: 1917. [Epub ahead of print]26(5):

Mitochondrial Dysfunction in Cardiovascular Diseases.

Han-Mo Yang.

  Mitochondrial dysfunction is increasingly recognized as a central contributor to the pathogenesis of cardiovascular diseases (CVDs), including heart failure, ischemic heart disease, hypertension, and cardiomyopathy. Mitochondria, known as the powerhouses of the cell, play a vital role in maintaining cardiac energy homeostasis, regulating reactive oxygen species (ROS) production and controlling cell death pathways. Dysregulated mitochondrial function results in impaired adenosine triphosphate (ATP) production, excessive ROS generation, and activation of apoptotic and necrotic pathways, collectively driving the progression of CVDs. This review provides a detailed examination of the molecular mechanisms underlying mitochondrial dysfunction in CVDs, including mutations in mitochondrial DNA (mtDNA), defects in oxidative phosphorylation (OXPHOS), and alterations in mitochondrial dynamics (fusion, fission, and mitophagy). Additionally, the role of mitochondrial dysfunction in specific cardiovascular conditions is explored, highlighting its impact on endothelial dysfunction, myocardial remodeling, and arrhythmias. Emerging therapeutic strategies targeting mitochondrial dysfunction, such as mitochondrial antioxidants, metabolic modulators, and gene therapy, are also discussed. By synthesizing recent advances in mitochondrial biology and cardiovascular research, this review aims to enhance understanding of the role of mitochondria in CVDs and identify potential therapeutic targets to improve cardiovascular outcomes.

Keywords:  cardiovascular disease; mitochondrial dynamics; mitochondrial dysfunction; oxidative stress

DOI:  https://doi.org/10.3390/ijms26051917
Int J Mol Sci. 2025 Feb 20. pii: 1803. [Epub ahead of print]26(5):

Role of Mitochondrial Dynamics in Skin Homeostasis: An Update.

Tao Quan, Ran Li, Ting Gao.

  Skin aging is the most prominent phenotype of host aging and is the consequence of a combination of genes and environment. Improving skin aging is essential for maintaining the healthy physiological function of the skin and the mental health of the human body. Mitochondria are vital organelles that play important roles in cellular mechanisms, including energy production and free radical balance. However, mitochondrial metabolism, mitochondrial dynamics, biogenesis, and degradation processes vary greatly in various cells in the skin. It is well known that mitochondrial dysfunction can promote the aging and its associated diseases of the skin, resulting in the damage of skin physiology and the occurrence of skin pathology. In this review, we summarize the important role of mitochondria in various skin cells, review the cellular responses to vital steps in mitochondrial quality regulation, mitochondrial dynamics, mitochondrial biogenesis, and mitochondrial phagocytosis, and describe their importance and specific pathways in skin aging.

Keywords:  mitochondria; oxidative stress; skin aging; ultraviolet radiation

DOI:  https://doi.org/10.3390/ijms26051803
Front Mol Biosci. 2025 ;12 1525103

Q-Der: a next-generation CoQ10 analogue supercharging neuroprotection by combating oxidative stress and enhancing mitochondrial function.

Matteo Micucci, Federico Gianfanti, Sabrina Donati Zeppa, Giosuè Annibalini, Barbara Canonico, Fabiana Fanelli, Roberta Saltarelli, Riham Osman, Mariele Montanari, Daniele Lopez, Gemma Nasoni, Giovanna Panza, Erik Bargagni, Francesca Luchetti, Michele Retini, Michele Mari, Giovanni Zappia, Vilberto Stocchi, Alessia Bartolacci, Sabrina Burattini, Michela Battistelli.

   Background: Mitochondrial dysfunction and oxidative stress are central mechanisms in the progression of neurodegenerative diseases. This study first evaluated the toxicity of Q-Der (Q10-diacetate), a derivative of Coenzyme Q10, in HT22 hippocampal neurons under normal and oxidative stress conditions.
Methods: HT22 cells were treated with Q-Der at 2.5, 5 and 10 µM with and without rotenone. Mitochondrial superoxide production (Mitosox), gene expression (via qRT-PCR), and protein levels (via Western blot) were measured. Morphological analyses were performed using transmission (TEM) and scanning (SEM) electron microscopes.
Results: Q-Der significantly reduced mitochondrial superoxide levels, particularly at 5 μM, and upregulated key mitochondrial biogenesis genes, including PGC-1α and TFAM. Additionally, it restored the expression of MT-ND1 and MT-COI, which were downregulated by rotenone. Western blot results showed a significant recovery in CV-ATP5A (complex V) expression (p < 0.05), preserving mitochondrial ATP production. Morphological analyses further confirmed Q-Der's ability to maintain cellular and mitochondrial structure under stress conditions.
Conclusion: These findings suggest that Q-Der is non-toxic under normal conditions and protects against oxidative stress, supporting its potential as a therapeutic agent for neurodegenerative diseases.

Keywords:  ATP synthesis; HT22 cells; Q-Der; coenzyme Q10; mitochondrial dysfunction; neuroprotection; oxidative stress; rotenone

DOI:  https://doi.org/10.3389/fmolb.2025.1525103
Inflammopharmacology. 2025 Mar 10.

Insulin resistance in Alzheimer's disease: signalling mechanisms and therapeutics strategies.

Mini Dahiya, Monu Yadav, Chetan Goyal, Anil Kumar.

   BACKGROUND: Alzheimer's disease (AD), one of the most common neurodegenerative disorders, is characterised by hallmark abnormalities such as amyloid-β plaques and neurofibrillary tangles (NFTs). Emerging evidence suggests that faulty insulin signalling contributes to these pathological features, impairing critical cellular and metabolic processes.
OBJECTIVE: This review aims to elucidate the role of insulin signalling in the central nervous system (CNS) under normal and pathological conditions and to explore therapeutic approaches targeting insulin pathways in AD and other neurodegenerative diseases.
METHODS: We reviewed studies highlighting the involvement of insulin-signalling pathways in neuronal health, with a particular focus on the key components-IRS, PI3K, Akt, and GSK-3β-predominantly expressed in cortical and hippocampal regions.
RESULTS: Insulin, an essential growth factor, regulates numerous cellular functions, including glucose metabolism, mitochondrial activity, oxidative stress response, autophagy, synaptic plasticity, and cognitive processes. Altered phosphorylation of signalling molecules in insulin pathways contributes to oxidative stress, inflammation, and the formation of AD hallmarks. Indirect modulators such as NF-κB and caspases further exacerbate neuronal damage, linking impaired insulin signalling to neurodegeneration.
CONCLUSION: Insulin signalling plays a crucial role in maintaining neuronal health and mitigating neurodegenerative processes. Targeting insulin pathways and associated molecules offers promising therapeutic avenues for AD and other neurodegenerative disorders.

Keywords:  Alzheimer’s disease; Insulin resistance; Insulin signalling; Treatment strategy

DOI:  https://doi.org/10.1007/s10787-025-01704-2
J Nanobiotechnology. 2025 Mar 11. 23(1): 202

Mitochondria-targeted nanovesicles for ursodeoxycholic acid delivery to combat neurodegeneration by ameliorating mitochondrial dysfunction.

Shizheng Zhang, Mengmeng Li, Yuan Li, Shike Yang, Jian Wang, Xiaoxiang Ren, Xiuhui Wang, Long Bai, Jianping Huang, Zhen Geng, Guosheng Han, Yibin Fang, Jiacan Su.

  Mitochondria are pivotal in sustaining oxidative balance and metabolic activity within neurons. It is well-established that mitochondrial dysfunction constitutes a fundamental pathogenic mechanism in neurodegeneration, especially in the context of Parkinson's disease (PD), this represents a promising target for therapeutic intervention. Ursodeoxycholic acid (UDCA), a clinical drug used for liver disease, possesses antioxidant and mitochondrial repair properties. Recently, it has gained attention as a potential therapeutic option for treating various neurodegenerative diseases. However, multiple barriers, including the blood-brain barrier (BBB) and cellular/mitochondrial membranes, significantly hinder the efficient delivery of therapeutic agents to the damaged neuronal mitochondria. Macrophage-derived nanovesicles (NVs), which can traverse the BBB in response to brain inflammation signals, have demonstrated promising tools for brain drug delivery. Nevertheless, natural nanovesicles inherently lack the ability to specifically target mitochondria. Herein, artificial NVs are loaded with UDCA and then functionalized with triphenylphosphonium (TPP) molecules, denoted as UDCA-NVs-TPP. These nanovesicles specifically accumulate in damaged neuronal mitochondria, reduce oxidative stress, and enhance ATP production by 42.62%, thereby alleviating neurotoxicity induced by 1-methyl-4-phenylpyridinium (MPP+). Furthermore, UDCA-loaded NVs modified with TPP successfully cross the BBB and accumulate in the striatum of PD mice. These nanoparticles significantly improve PD symptoms, as demonstrated by a 48.56% reduction in pole climb time, a 59.09% increase in hanging ability, and the restoration of tyrosine hydroxylase levels to normal, achieving remarkable therapeutic efficacy. Our work highlights the immense potential of these potent UDCA-loaded, mitochondria-targeting nanovesicles for efficient treatment of PD and other central neurodegenerative diseases.

Keywords:  BBB; MNVs; Mitochondrial dysfunction; Mitochondrial targeting; Neurodegenerative diseases; UDCA

DOI:  https://doi.org/10.1186/s12951-025-03258-5
J Alzheimers Dis. 2025 Mar 13. 13872877251321118

Vascular dysfunction in Alzheimer's disease: Exploring the potential of aerobic and resistance exercises as therapeutic strategies.

Larissa Alves, Debora Hashiguchi, Cássio Morais Loss, Henriette van Praag, Beatriz Monteiro Longo.

  Alzheimer's disease (AD) is the leading cause of morbidity and mortality worldwide, as a result of cognitive decline and neurological dysfunction. In AD, reduced cerebral blood flow and impaired vascularization result from capillary bed degeneration and decreased angiogenesis, as observed in both patients and animal models. Physical exercise is recognized as a potential intervention to delay AD progression and reduce disease risk. While most studies have focused on the benefits of aerobic exercise (AE), emerging evidence suggests that resistance exercise (RE) also exerts positive effects on overall health and cognitive function in aging and AD. However, a notable gap in knowledge remains regarding the effects of RE on cerebral blood flow and vascular structure. This review explores the processes by which AE and RE influence brain vascularization in aging and AD, including blood flow, endothelial function, angiogenesis and neurotrophic factor levels. Based on pre-clinical and clinical studies, we conclude that both AE and RE contribute to improved cerebral blood flow and vascular function, promoting vascular repair in the aging and AD-affected brain. By examining the relationship between exercise modalities and brain vascularization, this review expands knowledge regarding the processes underlying the neuroprotective effects of exercise in neurodegenerative and aging conditions.

Keywords:  Alzheimer's disease; aerobic exercise; cerebral vascularization; normal aging; resistance exercise

DOI:  https://doi.org/10.1177/13872877251321118
Free Radic Biol Med. 2025 Mar 10. pii: S0891-5849(25)00160-1. [Epub ahead of print]

5-Methoxytryptophan Attenuates Oxidative Stress-Induced Downregulation of PINK1 and Mitigates Mitochondrial Damage and Apoptosis in Cardiac Myocytes.

Chii-Ming Lee, Tung-Chun Chien, Juo-Shan Wang, Yu-Wei Chen, Chin-Yu Chen, Chen-Chin Kuo, Liang-Ting Chiang, Kenneth K Wu, Wan-Tseng Hsu.

  Mitochondrial dysfunction is a hallmark in the pathogenesis of various cardiovascular diseases. 5-Methoxytryptophan (5-MTP), an intrinsic amino acid metabolite, exerts cardioprotective effects potentially through the preservation of mitochondrial integrity. This study investigates the mechanisms and contexts in which 5-MTP positively impacts mitochondrial function using cultured human ventricular cardiomyocytes (HCMs) and HL-1 cardiac cells subjected to oxidative stress (OS). We first demonstrated that 5-MTP up-regulates the expression of PINK1, a key regulator of mitochondrial homeostasis. PINK1 knockdown attenuated the beneficial effects of 5-MTP on cardiomyocyte apoptosis. Furthermore, in cells exposed to OS, 5-MTP pretreatment led to a notable decrease in mitochondrial superoxide generation. Fluorescence imaging and network analysis showed that 5-MTP preserved mitochondrial membrane potential and enhanced mitochondrial network integrity. The reduction in the phosphorylation of dynamin-related protein 1, which is involved in mitochondrial fission, uncovered the role of 5-MTP in maintaining mitochondrial dynamics. Notably, 5-MTP attenuated OS-induced mitophagy, as evidenced by reduced mitophagy detection dye fluorescence and lower mitochondrial Parkin levels, suggesting that mechanisms beyond the PINK1/Parkin pathway are involved. Restoration of AKT phosphorylation and reduced mitochondrial Bax localization further revealed an additional pathway contributing to mitochondrial protection. Moreover, 5-MTP attenuated pro-apoptotic Bax levels and enhanced PINK1 expression in a rat model of ischemic cardiomyopathy, corroborating its cardioprotective role. Collectively, these findings demonstrate that 5-MTP mitigates mitochondrial dysfunction by integrating the roles of PINK1, AKT, and Bax, offering potential as a therapeutic agent to enhance cellular resilience in OS-driven mitochondrial damage.

Keywords:  5-Methoxytryptophan; AKT; Bax; PINK1; apoptosis; mitochondria; oxidative stress

DOI:  https://doi.org/10.1016/j.freeradbiomed.2025.03.010
Free Radic Biol Med. 2025 Mar 12. pii: S0891-5849(25)00162-5. [Epub ahead of print]

The Nuclear-Mitochondrial Crosstalk in Aging: From Mechanisms to Therapeutics.

Yifei Feng, Yan Lu.

  Aging is a complex physiological process characterized by an irreversible decline in tissue and cellular functions, accompanied by an increased risk of age-related diseases, including neurodegenerative, cardiovascular, and metabolic disorders. Central to this process are epigenetic modifications, particularly DNA methylation, which regulate gene expression and contribute to aging-related epigenetic drift. This drift is characterized by global hypomethylation and localized hypermethylation, impacting genomic stability and cellular homeostasis. Simultaneously, mitochondrial dysfunction, a hallmark of aging, manifests as impaired oxidative phosphorylation, excessive reactive oxygen species production, and mitochondrial DNA mutations, driving oxidative stress and cellular senescence. Emerging evidence highlights a bidirectional interplay between epigenetics and mitochondrial function. DNA methylation modulates the expression of nuclear genes governing mitochondrial biogenesis and quality control, while mitochondrial metabolites, such as acetyl-CoA and S-adenosylmethionine, reciprocally influence epigenetic landscapes. This review delves into the intricate nuclear-mitochondrial crosstalk, emphasizing its role in aging-related diseases and exploring therapeutic avenues targeting these interconnected pathways to counteract aging and promote health span extension.

Keywords:  Aging; DNA Methylation; Epigenetics; Mitochondrial Dysfunction

DOI:  https://doi.org/10.1016/j.freeradbiomed.2025.03.012
Molecules. 2025 Feb 21. pii: 1010. [Epub ahead of print]30(5):

27-Hydroxymangiferolic Acid Extends Lifespan and Improves Neurodegeneration in Caenorhabditis elegans by Activating Nuclear Receptors.

Xiaoyan Gao, Jing Yu, Yin Li, Hang Shi, Lijun Zhang, Minglv Fang, Ying Liu, Cheng Huang, Shengjie Fan.

  27-Hydroxymangiferolic acid (27-HMA) is a naturally occurring compound in mango fruits that exhibits diverse biological functions. Here, we show that 27-HMA activates the transcriptional activity of farnesoid X receptor (FXR), a nuclear receptor transcription factor, extending the lifespan and healthspan in Caenorhabditis elegans (C. elegans). Meanwhile, the longevity-promoting effect of 27-HMA was attenuated in the mutants of nhr-8 and daf-12, the FXR homologs, indicating that the longevity effects of 27-HMA in C. elegans may depend on nuclear hormone receptors (NHRs). Further analysis revealed potential associations between the longevity effects of 27-HMA and the insulin/insulin-like growth factor-1 signaling (IIS)/TORC1 pathway. Moreover, 27-HMA increased the toxin resistance of nematodes and activated the expression of detoxification genes, which rely on NHRs. Finally, 27-HMA improved the age-related neurodegeneration in Alzheimer's disease (AD) and Parkinson's disease (PD) C. elegans models. Taken together, our findings suggest that 27-HMA is a novel FXR agonist and may prolong lifespan and healthspan via activating NHRs.

Keywords:  27-hydroxymangiferolic acid; Alzheimer’s disease; Parkinson’s disease; detoxification; lifespan; nuclear receptor

DOI:  https://doi.org/10.3390/molecules30051010
J Nutr Biochem. 2025 Mar 06. pii: S0955-2863(25)00051-8. [Epub ahead of print] 109888

Iron metabolism and ferroptosis in health and diseases: the crucial role of mitochondria in meta-bolically active tissues.

Angela Catapano, Fabiano Cimmino, Lidia Petrella, Amelia Pizzella, Margherita D'Angelo, Katia Ambrosio, Francesca Marino, Annarita Sabbatini, Massimiliano Petrelli, Barbara Paolini, Lucio Lucchin, Gina Cavaliere, Luigia Cristino, Marianna Crispino, Giovanna Trinchese, Maria Pina Mollica.

  Iron is essential in various physiological processes, but its accumulation leads to oxidative stress and cell damage, thus iron homeostasis has to be tightly regulated. Ferroptosis is an iron-dependent non-apoptotic regulated cell death characterized by iron overload and ROS accumulation. Mitochondria are organelles playing a crucial role in iron metabolism and involved in ferroptosis. MitoNEET, a protein of mitochondrial outer membrane, is a key element in this process. Ferroptosis, altering iron levels in several metabolically active organs, is linked to several non-communicable diseases. For example, iron overload in the liver leads to hepatic fibrosis and cirrhosis, accelerating NAFLD progression, in the muscle cells contributes to oxidative damage leading to sarcopenia, and in the brain is associated to neurodegeneration. The aim of this review is to investigate the intricate balance of iron regulation focusing on the role of mitochondria and oxidative stress, and analyzing the ferroptosis implications in health and disease.

Keywords:  Ferroptosis; Iron; MitoNEET; Mitochondria; Obesity

DOI:  https://doi.org/10.1016/j.jnutbio.2025.109888
J Clin Aesthet Dermatol. 2025 Feb;18(2): 44-49

Reversing Glycation with a Dietary Supplement Containing Rosemary Extract.

Zoe Draelos, Vivian Bucay, Jacqueline Watchmaker, Giuseppe Valacchi.

Objective: The authors sought to explore the skin deglycation ability of rosemary extract dietary supplements to support skin health and improve the signs of skin aging.
Methods: A PubMed literature search for English-language articles on rosemary extract effects on glycation and skin aging in clinical and/or preclinical settings was conducted.
Results: Endogenous and exogenous glycative stress and reactive oxygen species lead to the accumulation of advanced glycation endproducts (AGEs), accelerating skin aging. Rosemary extract, and its active polyphenol, rosmarinic acid (RA), exhibit antiglycative and antioxidant effects, preventing AGE formation. Rosemary reduces reactive intermediates in the glycation pathway, decreases protein carbonylation, and protects against environmental stressors. Rosemary has shown potential in reversing glycation, benefiting skin health by protecting collagen and elastin. Both topical and oral delivery methods have been investigated and have shown to be beneficial. Manufacturing and extraction methods are critical in preserving essential and synergistic components of the extract when optimizing formulation development.
Limitations: As a narrative review, the selection of the literature was not fully comprehensive, thus introducing a potential for bias. However, our aim was to provide insights into the impacts of glycation and RA on skin quality and health.
Conclusion: Rosemary extract and RA appear to exhibit antiglycative effects, both interrupting AGE formation and AGE-protein crosslinks, making them promising compounds for skin health. However, further research is needed to fully understand their mechanisms and therapeutic potential.

Keywords: Glycative stress; advanced glycation endproducts (AGEs); antiglycative effects; antioxidant properties; nutraceuticals; rosemary extract; rosmarinic acid; skin aging; skin health
Biol Open. 2025 Mar 06. pii: bio.061815. [Epub ahead of print]

GSK3 coordinately regulates mitochondrial activity and nucleotide metabolism in quiescent oocytes.

Leah Eller, Lei Wang, Mehmet Oguz Gok, Helin Hocaoglu, Shenlu Qin, Parul Gupta, Matthew H Sieber.

  As cells transition between periods of growth and quiescence, their metabolic demands change. During this transition, cells must coordinate changes in mitochondrial function with the induction of biosynthetic processes. Mitochondrial metabolism and nucleotide biosynthesis are key rate-limiting factors in regulating early growth. However, it remains unclear what coordinates these mechanisms in developmental systems. Here, we show that during quiescence, as mitochondrial activity drops, nucleotide breakdown increases. However, at fertilization, mitochondrial oxidative metabolism and nucleotide biosynthesis are coordinately activated to support early embryogenesis. We have found that the serine/threonine kinase GSK3 is a key factor in coordinating mitochondrial metabolism with nucleotide biosynthesis during transitions between quiescence and growth. Silencing GSK3 in quiescent oocytes causes increased levels of mitochondrial activity and a shift in the levels of several redox metabolites. Interestingly, silencing GSK3 in quiescent oocytes also leads to a precocious induction of nucleotide biosynthesis in quiescent oocytes. Taken together, these data indicate that GSK3 functions to suppress mitochondrial oxidative metabolism and prevent the premature onset of nucleotide biosynthesis in quiescent eggs. These data reveal a key mechanism that coordinates mitochondrial function and nucleotide synthesis with fertilization.

Keywords:  Drosophila; Embryo; Metabolism; Mitochondria; Oocyte

DOI:  https://doi.org/10.1242/bio.061815