bims-mistre 2025-02-16 papers

bims-mistre

Biomed News

on Mito stress

Issue of 2025–02–16
nineteen papers selected by
Ellen Siobhan Mitchell, MitoQ

Mitochondrial Alterations, Oxidative Stress, and Therapeutic Implications in Alzheimer's Disease: A Narrative Review.
Antioxidant and Anti-Inflammatory Effects of Bioactive Compounds in Atherosclerosis.
Low doses of bisphenol F and S affect human ovarian granulosa cells by reducing the number of active mitochondria and ATP synthesis.
Microglial NLRP3 Inflammasomes in Alzheimer's Disease Pathogenesis: From Interaction with Autophagy/Mitophagy to Therapeutics.
A Comprehensive Review of the Contribution of Mitochondrial DNA Mutations and Dysfunction in Polycystic Ovary Syndrome, Supported by Secondary Database Analysis.
Protective Effects of Sulforaphane Preventing Inflammation and Oxidative Stress to Enhance Metabolic Health: A Narrative Review.
Exploring the Link Between Telomeres and Mitochondria: Mechanisms and Implications in Different Cell Types.
Redox imbalance and hypoxia-inducible factors: a multifaceted crosstalk.
Apigenin Ameliorates Insulin Resistance in 3T3-L1 Adipocytes: Establishment of a New Insulin Resistance Model Induced by Combined Treatments.
Impact of physical activity on physical function, mitochondrial energetics, ROS production, and Ca2+ handling across the adult lifespan in men.
Exploring the role of curcumin in mitigating oxidative stress to alleviate lipid metabolism disorders.
NLRP3 inflammasome in health and disease (Review).
Postbiotics as a Therapeutic Tool in Alzheimer's Disease: Insights into Molecular Pathways and Neuroprotective Effects.
Diverse routes to mitophagy governed by ubiquitylation and mitochondrial import.
The Role of Gut Microbiota-Derived Trimethylamine N-Oxide in the Pathogenesis and Treatment of Mild Cognitive Impairment.
Leptin Resistance and Cardiometabolic Disorders: Bridging Molecular Pathways, Genetic Variants, and Therapeutic Innovation.
The Pathophysiological Role of Mitochondria-associated Membranes in Coronary Artery Disease and Atherosclerosis.
Epigallocatechin Gallate (EGCG): Pharmacological Properties, Biological Activities and Therapeutic Potential.
Assisted Reproduction Technologies (ART): Impact of Mitochondrial (Dys)function and Antioxidant Therapy.

Cells. 2025 Feb 06. pii: 229. [Epub ahead of print]14(3):

Mitochondrial Alterations, Oxidative Stress, and Therapeutic Implications in Alzheimer's Disease: A Narrative Review.

Erica Spina, Riccardo Rocco Ferrari, Elisa Pellegrini, Mauro Colombo, Tino Emanuele Poloni, Antonio Guaita, Annalisa Davin.

  The relationship between aging, mitochondrial dysfunction, neurodegeneration, and the onset of Alzheimer's disease (AD) is a complex area of study. Aging is the primary risk factor for AD, and it is associated with a decline in mitochondrial function. This mitochondrial dysfunction is believed to contribute to the neurodegenerative processes observed in AD. Neurodegeneration in AD is characterized by the progressive loss of synapses and neurons, particularly in regions of the brain involved in memory and cognition. It is hypothesized that mitochondrial dysfunction plays a pivotal role by disrupting cellular energy metabolism and increasing the production of reactive oxygen species (ROS), which can damage cellular components and exacerbate neuronal loss. Despite extensive research, the precise molecular pathways linking mitochondrial dysfunction to AD pathology are not fully understood. Various hypotheses have been proposed, including the mitochondrial cascade hypothesis, which suggests that mitochondrial dysfunction is an early event in AD pathogenesis that triggers a cascade of cellular events leading to neurodegeneration. With this narrative review, we aim to summarize some specific issues in the literature on mitochondria and their involvement in AD onset, with a focus on the development of therapeutical strategies targeting the mitochondria environment and their potential application for the treatment of AD itself.

Keywords:  Alzheimer’s disease; aging; mitochondria; mitochondrial dysfunction

DOI:  https://doi.org/10.3390/cells14030229
Int J Mol Sci. 2025 Feb 06. pii: 1379. [Epub ahead of print]26(3):

Antioxidant and Anti-Inflammatory Effects of Bioactive Compounds in Atherosclerosis.

Ştefan Horia Roşian, Ioana Boarescu, Paul-Mihai Boarescu.

  Atherosclerosis, a chronic inflammatory disease characterized by the accumulation of lipids and immune cells within arterial walls, remains a leading cause of cardiovascular morbidity and mortality worldwide. Oxidative stress and inflammation are central to its pathogenesis, driving endothelial dysfunction, foam cell formation, and plaque instability. Emerging evidence highlights the potential of bioactive compounds with antioxidant and anti-inflammatory properties to mitigate these processes and promote vascular health. This review explores the mechanisms through which bioactive compounds-such as polyphenols, carotenoids, flavonoids, omega-3 fatty acids, coenzyme Q10, and other natural compounds-modulate oxidative stress and inflammation in atherosclerosis. It examines their effects on key molecular pathways, including the inhibition of reactive oxygen species (ROS) production, suppression of nuclear factor-κB (NF-κB), and modulation of inflammatory cytokines. By integrating current knowledge, this review underscores the therapeutic potential of dietary and supplemental bioactive compounds as complementary strategies for managing atherosclerosis, paving the way for future research and clinical applications.

Keywords:  anti-inflammatory; antioxidant; atherosclerosis; bioactive compound

DOI:  https://doi.org/10.3390/ijms26031379
Toxicol Lett. 2025 Feb 08. pii: S0378-4274(25)00017-7. [Epub ahead of print]405 41-50

Low doses of bisphenol F and S affect human ovarian granulosa cells by reducing the number of active mitochondria and ATP synthesis.

Paulina Głód, Weronika Marynowicz, Joanna Homa, Joanna Smoleniec, Dawid Maduzia, Anna Ptak.

  Bisphenols (BPs) are a group of environmental pollutants mainly represented by bisphenol S (BPS) and F (BPF). In ovaries, BPs can accumulate in follicular fluid (FF), changing the follicular microenvironment and simultaneously affecting ovarian granulosa cells (GCs) function. In the present study, we determined the effects of BPS and BPF on oxidative stress and mitochondrial function in human ovarian GCs. Single, short-term treatment with BPs at doses reflecting their concentrations in FF (10 nM) did not affect reactive oxygen species (ROS) levels but induced mitochondrial membrane depolarization. BPF-induced mitophagy decreased the number of active mitochondria and consequently reduced the ATP production rate. The observed changes did not translate into lowered viability of GCs, but long-term treatment with BPF influenced the intrinsic apoptosis pathway by increasing caspase 9 activity without affecting apoptosis. GCs are crucial for ovarian function as they produce primary steroid hormones and regulate oocyte maturation and follicle growth. Mitochondrial dysfunction caused by BPs, manifesting as reduced ATP production in GCs, can directly cause ovarian disorders such as infertility. Therefore, this study highlights the significance of investigating the effects of BPs on reproductive health.

Keywords:  Apoptosis; Bisphenol S and F; Human ovarian granulosa cells; IGF-1; Mitochondrial function; Mitophagy

DOI:  https://doi.org/10.1016/j.toxlet.2025.02.002
Mol Neurobiol. 2025 Feb 14.

Microglial NLRP3 Inflammasomes in Alzheimer's Disease Pathogenesis: From Interaction with Autophagy/Mitophagy to Therapeutics.

Gunel Ayyubova, Leelavathi N Madhu.

  The nucleotide-binding oligomerization domain-like receptor pyrin domain-containing 3 (NLRP3) inflammasome, discovered 20 years ago, is crucial in controlling innate immune reactions in Alzheimer's disease (AD). By initiating the release of inflammatory molecules (including caspases, IL-1β, and IL-18), the excessively activated inflammasome complex in microglia leads to chronic inflammation and neuronal death, resulting in the progression of cognitive deficiencies. Even though the involvement of NLRP3 has been implicated in neuroinflammation and widely explored in several studies, there are plenty of controversies regarding its precise roles and activation mechanisms in AD. Another prominent feature of AD is impairment in microglial autophagy, which can be either the cause or the consequence of NLRP3 activation and contributes to the aggregation of misfolded proteins and aberrant chronic inflammatory state seen in the disease course. Studies also demonstrate that intracellular buildup of dysfunctional and damaged mitochondria due to defective mitophagy enhances inflammasome activation, further suggesting that restoration of impaired autophagy and mitophagy can effectively suppress it, thereby reducing inflammation and protecting microglia and neurons. This review is primarily focused on the role of NLRP3 inflammasome in the etiopathology of AD, its interactions with microglial autophagy/mitophagy, and the latest developments in NLRP3 inflammasome-targeted therapeutic interventions being implicated for AD treatment.

Keywords:  Alzheimer’s disease; Autophagy; Microglia; Mitophagy; NLRP3 inflammasome

DOI:  https://doi.org/10.1007/s12035-025-04758-z
Int J Mol Sci. 2025 Jan 29. pii: 1172. [Epub ahead of print]26(3):

A Comprehensive Review of the Contribution of Mitochondrial DNA Mutations and Dysfunction in Polycystic Ovary Syndrome, Supported by Secondary Database Analysis.

Hiroshi Kobayashi, Sho Matsubara, Chiharu Yoshimoto, Hiroshi Shigetomi, Shogo Imanaka.

  Polycystic ovary syndrome (PCOS) is a common endocrine disorder affecting women of reproductive age characterized by a spectrum of clinical, metabolic, reproductive, and psychological abnormalities. This syndrome is associated with significant long-term health risks, necessitating elucidation of its pathophysiology, early diagnosis, and comprehensive management strategies. Several contributory factors in PCOS, including androgen excess and insulin resistance, collectively enhance oxidative stress, which subsequently leads to mitochondrial dysfunction. However, the precise mechanisms through which oxidative stress induces mitochondrial dysfunction remain incompletely understood. Comprehensive searches of electronic databases were conducted to identify relevant studies published up to 30 September 2024. Mitochondria, the primary sites of reactive oxygen species (ROS) generation, play critical roles in energy metabolism and cellular homeostasis. Oxidative stress can inflict damage on components, including lipids, proteins, and DNA. Damage to mitochondrial DNA (mtDNA), which lacks efficient repair mechanisms, may result in mutations that impair mitochondrial function. Dysfunctional mitochondrial activity further amplifies ROS production, thereby perpetuating oxidative stress. These disruptions are implicated in the complications associated with the syndrome. Advances in genetic analysis technologies, including next-generation sequencing, have identified point mutations and deletions in mtDNA, drawing significant attention to their association with oxidative stress. Emerging data from mtDNA mutation analyses challenge conventional paradigms and provide new insights into the role of oxidative stress in mitochondrial dysfunction. We are rethinking the pathogenesis of PCOS based on these database analyses. In conclusion, this review explores the intricate relationship between oxidative stress, mtDNA mutations, and mitochondrial dysfunction, offers an updated perspective on the pathophysiology of PCOS, and outlines directions for future research.

Keywords:  mitochondrial DNA copy number; mitochondrial DNA mutations; oxidative stress; polycystic ovary syndrome; replication errors

DOI:  https://doi.org/10.3390/ijms26031172
Nutrients. 2025 Jan 24. pii: 428. [Epub ahead of print]17(3):

Protective Effects of Sulforaphane Preventing Inflammation and Oxidative Stress to Enhance Metabolic Health: A Narrative Review.

Inês Alves, Edilene Maria Queiroz Araújo, Louise T Dalgaard, Sharda Singh, Elisabet Børsheim, Eugenia Carvalho.

  The worldwide obesity epidemic has led to a drastic increase in diabetes and cardiovascular disease in younger generations. Further, maintaining metabolic health during aging is frequently a challenge due to poor diets and decreased mobility. In this setting, bioactive nutrients that are naturally occurring antioxidants, such as sulforaphane (SFN), are of high nutritional interest. SFN, a bioactive compound that is present in cruciferous vegetables, is a molecule that protects cells from cytotoxic damage and mitigates oxidative stress, protecting against disease. It exerts its action through the activation of the transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2). Many studies have been performed in animals and humans to evaluate its effects on cancer, brain health, and neurodegenerative disorders. However, fewer clinical studies have been performed to evaluate its effects on insulin resistance and the development of type 2 diabetes mellitus (T2DM) across the lifespan. Given that, in some parts of the world, particularly in Europe, the population is growing older at a significant rate, it is crucial to promote healthy habits (healthy foods, dietary pattern, precision nutrition, and physical activity) from an early stage in life and across the lifespan to avoid debilitating health conditions occurring during adulthood and aging. Thus, in this narrative review, we discuss the protective effects of SFN supplementation on inflammatory and oxidative stress pathways and relate them to metabolic disease.

Keywords:  Nrf2; healthy aging; inflammation and oxidative stress; metabolic diseases; metabolic syndrome; nutraceutical; sulforaphane

DOI:  https://doi.org/10.3390/nu17030428
Int J Mol Sci. 2025 Jan 24. pii: 993. [Epub ahead of print]26(3):

Exploring the Link Between Telomeres and Mitochondria: Mechanisms and Implications in Different Cell Types.

Graziana Assalve, Paola Lunetti, Maria Santa Rocca, Ilaria Cosci, Andrea Di Nisio, Alberto Ferlin, Vincenzo Zara, Alessandra Ferramosca.

  Telomeres protect chromosome ends from damage, but they shorten with each cell division due to the limitations of DNA replication and are further affected by oxidative stress. This shortening is a key feature of aging, and telomerase, an enzyme that extends telomeres, helps mitigate this process. Aging is also associated with mitochondrial dysfunction, leading to increased reactive oxygen species (ROS) that exacerbate cellular damage and promote apoptosis. Elevated ROS levels can damage telomeres by oxidizing guanine and disrupting their regulation. Conversely, telomere damage impacts mitochondrial function, and activation of telomerase has been shown to reverse this decline. A critical link between telomere shortening and mitochondrial dysfunction is the DNA damage response, which activates the tumor suppressor protein p53, resulting in reduced mitochondrial biogenesis and metabolic disruptions. This highlights the bidirectional relationship between telomere maintenance and mitochondrial function. This review explores the complex interactions between telomeres and mitochondria across various cell types, from fibroblasts to sperm cells, shedding light on the interconnected mechanisms underlying aging and cellular function.

Keywords:  mitochondria; reactive oxygen species (ROS); telomerase; telomere; telomere length

DOI:  https://doi.org/10.3390/ijms26030993
FEBS J. 2025 Feb 11.

Redox imbalance and hypoxia-inducible factors: a multifaceted crosstalk.

Ravi, Jogender Singh.

  Redox homeostasis, the delicate balance between oxidative and reductive processes, is crucial for cellular function and overall organismal health. At the molecular level, cells need to maintain a fine balance between the levels of reactive oxygen species (ROS) and reducing equivalents such as glutathione and nicotinamide adenine dinucleotide phosphate. The perturbation of redox homeostasis due to excessive ROS production leads to oxidative stress that can damage lipids, proteins, and nucleic acids. Conversely, an overly reduced cellular environment due to overabundant reducing equivalents results in reductive stress, which also interferes with important cellular signaling and physiological processes. Disrupted redox homeostasis is linked to various pathological conditions, including neurodegenerative diseases, inflammatory diseases, cancer, and cardiovascular diseases. Cells employ diverse mechanisms to manage redox imbalance. The hypoxia response pathway, mediated by hypoxia-inducible factors and responsible for sensing and defending against low oxygen levels, plays a vital role in maintaining redox homeostasis. In this review, we highlight the complex and multifaceted crosstalk between hypoxia-inducible factors and redox homeostasis and discuss avenues for future research. Understanding the molecular mechanisms that link hypoxia-inducible factors to oxidative and reductive stresses is essential for comprehending several pathological conditions associated with hypoxia and redox imbalance.

Keywords:  HIF‐1; antioxidants; oxidative stress; reactive oxygen species; reductive stress

DOI:  https://doi.org/10.1111/febs.70013
Mol Nutr Food Res. 2025 Feb 13. e202400545

Apigenin Ameliorates Insulin Resistance in 3T3-L1 Adipocytes: Establishment of a New Insulin Resistance Model Induced by Combined Treatments.

Xiaoxuan Guo, Bing Xia, Sha Liu, Ying Dong, Yongzhong Qian, Jing Qiu.

  Adipose tissue dysfunction due to insulin resistance (IR) plays a central role in the development of metabolic diseases. Obesity-associated IR greatly attributes to low-grade inflammation and high circulating levels of FFAs and sugar. 3T3-L1 adipocytes exposed to a mixture of TNF-α, fructose, and palmitate acid for 24 h were validated as a model to simulate the pathogenesis of IR in obese people under a high-fat-fructose diet. Results show that the combined induction medium (CIM) successfully induced IR in 3T3-L1 adipocytes by impairing insulin signaling pathway. In the meantime, MAPK (JNK, ERK) pathway and NFκB p65 were activated, which are signs of inflammation response. Moreover, CIM caused mitochondrial dysfunction and oxidative stress. In addition, endoplasmic reticulum stress (ER stress) was evoked by CIM through activating IRE1α/XBP1s, eIF2α, and ATF6. Apigenin could efficiently relieve IR in adipocytes through sensitizing insulin signaling pathway, exerting antioxidant activity, blocking the NFκB pathway, and suppressing ER stress. The present study may provide new tools in discovering preventive and intervention strategies for IR caused by low-grade inflammation and high-fat-fructose diets and provide a basis for the application of apigenin in IR and other IR-related diseases.

Keywords:  TNF‐α; adipocyte; apigenin; fructose; insulin resistance; palmitate acid

DOI:  https://doi.org/10.1002/mnfr.202400545
Cell Rep Med. 2025 Feb 06. pii: S2666-3791(25)00041-2. [Epub ahead of print] 101968

Impact of physical activity on physical function, mitochondrial energetics, ROS production, and Ca2+ handling across the adult lifespan in men.

Marina Cefis, Vincent Marcangeli, Rami Hammad, Jordan Granet, Jean-Philippe Leduc-Gaudet, Pierrette Gaudreau, Caroline Trumpff, Qiuhan Huang, Martin Picard, Mylène Aubertin-Leheudre, Marc Bélanger, Richard Robitaille, José A Morais, Gilles Gouspillou.

  Aging-related muscle atrophy and weakness contribute to loss of mobility, falls, and disability. Mitochondrial dysfunction is widely considered a key contributing mechanism to muscle aging. However, mounting evidence positions physical activity as a confounding factor, making unclear whether muscle mitochondria accumulate bona fide defects with aging. To disentangle aging from physical activity-related mitochondrial adaptations, we functionally profiled skeletal muscle mitochondria in 51 inactive and 88 active men aged 20-93. Physical activity status confers partial protection against age-related decline in physical performance. Mitochondrial respiration remains unaltered in active participants, indicating that aging per se does not alter mitochondrial respiratory capacity. Mitochondrial reactive oxygen species (ROS) production is unaffected by aging and higher in active participants. In contrast, mitochondrial calcium retention capacity decreases with aging regardless of physical activity and correlates with muscle mass, performance, and the stress-responsive metabokine/mitokine growth differentiation factor 15 (GDF15). Targeting mitochondrial calcium handling may hold promise for treating aging-related muscle impairments.

Keywords:  calcium retention capacity; functional capacities; intermuscular fat accumulation; mitochondria; mitochondrial permeability transition pore; muscle atrophy and weakness; physical performance; reactive oxygen species; sarcopenia; skeletal muscle aging

DOI:  https://doi.org/10.1016/j.xcrm.2025.101968
Front Pharmacol. 2025 ;16 1517174

Exploring the role of curcumin in mitigating oxidative stress to alleviate lipid metabolism disorders.

Maojun Cheng, Fang Ding, Liyang Li, Changmao Dai, Xiaolan Sun, Jia Xu, Feier Chen, Mingxiu Li, Xueping Li.

  Lipid metabolism plays a crucial role in maintaining homeostasis and overall health, as lipids are essential molecules involved in bioenergetic processes. An increasing body of research indicates that disorders of lipid metabolism can contribute to the development and progression of various diseases, including hyperlipidemia, obesity, non-alcoholic fatty liver disease (NAFLD), diabetes mellitus, atherosclerosis, and cancer, potentially leading to poor prognoses. The activation of the oxidative stress pathway disrupts lipid metabolism and induces cellular stress, significantly contributing to metabolic disorders. A well-documented crosstalk and interconnection between these metabolic disorders exists. Consequently, researchers have sought to identify antioxidant-rich substances in readily accessible everyday foods for potential use as complementary therapies. Curcumin, known for its anti-inflammatory and antioxidant properties, has been shown to enhance cellular antioxidant activity, mitigate oxidative stress, and alleviate lipid metabolism disorders by reducing reactive oxygen species (ROS) accumulation. These effects include decreasing fat deposition, increasing fatty acid uptake, and improving insulin sensitivity. A review of the existing literature reveals numerous studies emphasizing the role of curcumin in the prevention and management of metabolic diseases. Curcumin influences metabolic disorders through multiple mechanisms of action, with the oxidative stress pathway playing a central role in various lipid metabolism disorders. Thus, we aimed to elucidate the role of curcumin in various metabolic disorders through a unified mechanism of action, offering new insights into the prevention and treatment of metabolic diseases. Firstly, this article provides a brief overview of the basic pathophysiological processes of oxidative stress and lipid metabolism, as well as the role of oxidative stress in the pathogenesis of lipid metabolism disorders. Notably, the article reviews the role of curcumin in mitigating oxidative stress and in preventing and treating diseases associated with lipid metabolism disorders, including hyperlipidemia, non-alcoholic fatty liver disease (NAFLD), atherosclerosis, obesity, and diabetes, thereby highlighting the therapeutic potential of curcumin in lipid metabolism-related diseases.

Keywords:  NAFLD; atherosclerosis; curcumin; diabetes; hyperlipidemia; lipid metabolism disorders; obesity; oxidative stress

DOI:  https://doi.org/10.3389/fphar.2025.1517174
Int J Mol Med. 2025 03;pii: 48. [Epub ahead of print]55(3):

NLRP3 inflammasome in health and disease (Review).

Haoran Wang, Li Ma, Weiran Su, Yangruoyu Liu, Ning Xie, Jun Liu.

  Activation of inflammasomes is the activation of inflammation‑related caspase mediated by the assembly signal of multi‑protein complex and the maturity of inflammatory factors, such as IL‑1β and IL‑18. Among them, the Nod‑like receptor family pyrin domain containing 3 (NLRP3) inflammasome is the most thoroughly studied type of inflammatory corpuscle at present, which is involved in the occurrence and development of numerous human diseases. Therefore, targeting the NLRP3 inflammasome has become the focus of drug development for related diseases. In this paper, the research progress of the NLRP3 inflammasome in recent years is summarized, including the activation and regulation of NLRP3 and its association with diseases. A deep understanding of the regulatory mechanism of NLRP3 will be helpful to the discovery of new drug targets and the development of therapeutic drugs.

Keywords:  NLRP3 inflammasome; cell organ; disease; gene therapy; inhibitor; ion flow; metabolic regulation

DOI:  https://doi.org/10.3892/ijmm.2025.5489
Ageing Res Rev. 2025 Feb 06. pii: S1568-1637(25)00031-5. [Epub ahead of print] 102685

Postbiotics as a Therapeutic Tool in Alzheimer's Disease: Insights into Molecular Pathways and Neuroprotective Effects.

Garry Hunjan, Khadga Raj Aran.

  Alzheimer's disease (AD) is a progressive neurodegenerative disease, characterized by oxidative stress, neuroinflammation, mitochondrial dysfunction, neurotransmitter imbalance, tau hyperphosphorylation, and amyloid beta (Aβ) accumulation in brain regions. The gut microbiota (GM) has a major impact on brain function due to its bidirectional interaction with the gut through the gut-brain axis. The gut dysbiosis has been associated with neurological disorders, emphasizing the importance of gut homeostasis in maintaining appropriate brain function. The changes in the composition of microbiomes influence neuroinflammation and Aβ accumulation by releasing pro-inflammatory cytokines, decreasing gut and blood-brain barrier (BBB) integrity, and microglial activation in the brain. Postbiotics, are bioactive compounds produced after fermentation, have been shown to provide several health benefits, particularly in terms of neuroinflammation and cognitive alterations associated with AD. Several research studies on animal models and human have successfully proven the effects of postbiotics on enhancing cognition and memory in experimental animals. This article explores the protective effects of postbiotics on cellular mechanisms responsible for AD pathogenesis and studies highlighting the influence of postbiotics as a total combination and specific compounds, including short-chain fatty acids (SCFAs). In addition, postbiotics act as a promising option for future research to deal with AD's progressive nature and improve an individual's life quality using microbiota modulation.

Keywords:  Alzheimer’s disease; Dysbiosis; Neuroinflammation; Oxidative stress; Postbiotics; Probiotics

DOI:  https://doi.org/10.1016/j.arr.2025.102685
Trends Cell Biol. 2025 Feb 07. pii: S0962-8924(25)00003-0. [Epub ahead of print]

Diverse routes to mitophagy governed by ubiquitylation and mitochondrial import.

Michael J Clague, Sylvie Urbé.

  The selective removal of mitochondria by mitophagy proceeds via multiple mechanisms and is essential for human well-being. The PINK1/Parkin and NIX/BNIP3 pathways are strongly linked to mitochondrial dysfunction and hypoxia, respectively. Both are regulated by ubiquitylation and mitochondrial import. Recent studies have elucidated how the ubiquitin kinase PINK1 acts as a sensor of mitochondrial import stress through stable interaction with a mitochondrial import supercomplex. The stability of BNIP3 and NIX is regulated by the SCFFBXL4 ubiquitin ligase complex. Substrate recognition requires an adaptor molecule, PPTC7, whose availability is limited by mitochondrial import. Unravelling the functional implications of each mode of mitophagy remains a critical challenge. We propose that mitochondrial import stress prompts a switch between these two pathways.

Keywords:  BNIP3; FBXL4; PINK1; PPTC7; mitophagy; ubiquitin

DOI:  https://doi.org/10.1016/j.tcb.2025.01.003
Int J Mol Sci. 2025 Feb 06. pii: 1373. [Epub ahead of print]26(3):

The Role of Gut Microbiota-Derived Trimethylamine N-Oxide in the Pathogenesis and Treatment of Mild Cognitive Impairment.

Haihua Xie, Jia Jiang, Sihui Cao, Xuan Xu, Jingyin Zhou, Ruhan Zhang, Bo Huang, Penghui Lu, Liang Peng, Mi Liu.

  Mild cognitive impairment (MCI) represents a transitional stage between normal aging and dementia, often considered critical for dementia prevention. Despite its significance, no effective clinical treatment for MCI has yet been established. Emerging evidence has demonstrated a strong association between trimethylamine-N-oxide (TMAO), a prominent metabolite derived from the gut microbiota, and MCI, highlighting its potential as a biomarker and therapeutic target. TMAO has been implicated in increasing MCI risk through its influence on factors such as hypertension, cardiovascular disease, depression, diabetes, and stroke. Moreover, it contributes to MCI by promoting oxidative stress, disrupting the blood-brain barrier, impairing synaptic plasticity, inducing inflammation, causing mitochondrial metabolic disturbances, and facilitating abnormal protein aggregation. This review further explores therapeutic strategies targeting TMAO to mitigate MCI progression.

Keywords:  brain disease; gut microbiota; mechanism; metabolism; mild cognitive impairment; risk factor; therapy; trimethylamine-N-oxide

DOI:  https://doi.org/10.3390/ijms26031373
Curr Cardiol Rev. 2025 Feb 07.

Leptin Resistance and Cardiometabolic Disorders: Bridging Molecular Pathways, Genetic Variants, and Therapeutic Innovation.

Prashanjit Roy, Rishi Kant, Amandeep Kaur, Hardik Kumar, Ranjeet Kumar.

  Leptin, a hormone produced by fat cells, is crucial for regulating energy equilibrium, managing body mass, and influencing metabolic and cardiovascular well-being. Leptin decreases appetite, boosts energy usage, and has a significant impact on glucose metabolism by primarily activating the JAK2/STAT3 signaling pathway in the hypothalamus. Obesity leads to the development of leptin resistance, which is marked by high levels of leptin in the bloodstream and a decreased responsiveness to its signals. This leads to increased food consumption, weight gain, and metabolic issues, such as type 2 diabetes (T2DM) and cardiovascular disease (CVD). This study explores the many roles of leptin in metabolic regulation, with a specific emphasis on its interaction with insulin and its impact on peripheral organs like the pancreas, liver, and muscles. Leptin resistance worsens chronic inflammation, oxidative stress, endothelial dysfunction, and insulin resistance, all of which are strongly linked to the development of cardiovascular disease (CVD). Moreover, there is a correlation between genetic variations in the leptin receptor (LEPR) gene and a higher susceptibility to stroke and other cardiovascular issues. Therapeutic interventions, such as leptin replacement therapy, have demonstrated potential in the treatment of congenital leptin insufficiency and lipodystrophy while also enhancing glycaemic control, lipid profiles, and neuroendocrine function. Recent studies have indicated that manipulating leptin levels or enhancing its responsiveness by specific treatments, such as chemical chaperones and inhibitors of negative regulators like SOCS3 and PTP1B, might potentially restore the efficacy of leptin.

Keywords:  CVD; Leptin; hypertension; metabolism.; obesity; resistance

DOI:  https://doi.org/10.2174/011573403X356019250118170444
Curr Med Chem. 2025 Feb 12.

The Pathophysiological Role of Mitochondria-associated Membranes in Coronary Artery Disease and Atherosclerosis.

Junyan Zhang, Zhongxiu Chen, Li Rao, Yong He.

  Mitochondria-associated membranes (MAMs) are pivotal in cellular homeostasis, mediating communication between the endoplasmic reticulum and mitochondria. They are increasingly recognized for their role in atherosclerosis and coronary artery disease (CAD). This review delves into the cellular perspective of MAMs' impact on atherosclerosis and CAD, highlighting their influence on disease progression and the potential for therapeutic intervention. MAMs are implicated in key pathophysiological processes such as the generation of reactive oxygen species, calcium homeostasis, myocardial ischemia-reperfusion injury, autophagy, lipid synthesis and transport, and energy metabolism-fundamental to the development and progression of atherosclerosis and CAD. The complex interplay of MAMs with these pathological processes underscores their potential as therapeutic targets. This review synthesizes current understanding and emphasizes the need for further research to elucidate the multifaceted roles of MAMs in atherosclerosis and CAD, offering avenues for developing novel strategies aimed at improving mitochondrial health and mitigating the impact of these conditions.

Keywords:  Mitochondria-associated membranes (MAMs); atherosclerosis; autophagy; calcium homeostasis; coronary artery disease (CAD); ischemia-reperfusion injury; reactive oxygen species (ROS)

DOI:  https://doi.org/10.2174/0109298673343245250128093845
Molecules. 2025 Feb 01. pii: 654. [Epub ahead of print]30(3):

Epigallocatechin Gallate (EGCG): Pharmacological Properties, Biological Activities and Therapeutic Potential.

Lucia Capasso, Luigi De Masi, Carmina Sirignano, Viviana Maresca, Adriana Basile, Angela Nebbioso, Daniela Rigano, Paola Bontempo.

  Epigallocatechin gallate (EGCG), the predominant catechin in green tea, comprises approximately 50% of its total polyphenol content and has garnered widespread recognition for its significant therapeutic potential. As the principal bioactive component of Camellia sinensis, EGCG is celebrated for its potent antioxidant, anti-inflammatory, cardioprotective, and antitumor properties. The bioavailability and metabolism of EGCG within the gut microbiota underscore its systemic effects, as it is absorbed in the intestine, metabolized into bioactive compounds, and transported to target organs. This compound has been shown to influence key physiological pathways, particularly those related to lipid metabolism and inflammation, offering protective effects against a variety of diseases. EGCG's ability to modulate cell signaling pathways associated with oxidative stress, apoptosis, and immune regulation highlights its multifaceted role in health promotion. Emerging evidence underscores EGCG's therapeutic potential in preventing and managing a range of chronic conditions, including cancer, cardiovascular diseases, neurodegenerative disorders, and metabolic syndromes. Given the growing prevalence of lifestyle-related diseases and the increasing interest in natural compounds, EGCG presents a promising avenue for novel therapeutic strategies. This review aims to summarize current knowledge on EGCG, emphasizing its critical role as a versatile natural bioactive agent with diverse clinical applications. Further exploration in both experimental and clinical settings is essential to fully unlock its therapeutic potential.

Keywords:  biological activity; epigallocatechin gallate; human pathologies; pharmacological activity; preventive activity

DOI:  https://doi.org/10.3390/molecules30030654
Animals (Basel). 2025 Jan 21. pii: 289. [Epub ahead of print]15(3):

Assisted Reproduction Technologies (ART): Impact of Mitochondrial (Dys)function and Antioxidant Therapy.

Filipa C Ferreira, José Teixeira, Fernando Lidon, Fernando Cagide, Fernanda Borges, Rosa M L N Pereira.

  In the last decades, major changes in ecosystems related to industrial development and environmental modifications have had a direct impact on mammalian fertility, as well as on biodiversity. It is widely demonstrated that all these changes impair reproductive function. Several studies have connected the increase of reactive oxygen species (ROS) generated in mitochondria to the recently identified decline of fertility due to various factors, including heat stress. The study of antioxidants, and especially of mitochondria targeted antioxidants, has been focused on identifying more efficient and less toxic therapies that could circumvent fertility problems. These antioxidants can be derived from natural compounds in the diet and delivered to the mitochondria in more effective forms, providing a much more natural therapy. The use of mitochondriotropic diet-based antioxidants in assisted reproductive technologies (ART) may be an important way to overcome low fertility, allowing the conservation of animal biodiversity and productivity. This paper provides a concise review of the current state of the art on this topic, with a particular focus on the antioxidants mitoquinone, AntiOxBEN2, AntiOxCIN4, urolithin A and piperine, and their effects on bovine and other animal species.

Keywords:  antioxidants; embryos; fertility; gamete; mitochondria; oxidative stress; reproduction

DOI:  https://doi.org/10.3390/ani15030289