bims-mistre 2025-07-27 papers

bims-mistre

Biomed News

on Mito stress

Issue of 2025–07–27
nine papers selected by
Ellen Siobhan Mitchell, MitoQ

Biochanin A as a potential agent in the disease therapy via mitochondria-mediated mechanisms.
Sirtuins in mitophagy: key gatekeepers of mitochondrial quality.
Stressful situations: molecular insights on mitochondrial quality control pathways.
Mitochondrial cardiovascular diseases: molecular mechanisms, multi-omics exploration and therapeutic strategies.
Pharmacologic interventions targeting ovarian aging, cancer, and mitochondrial dysfunction: An updated evidence.
Black Tea Aqueous Extract Extends Yeast Longevity via Antioxidant Gene Activation: Transcriptomic Analysis of Anti-Aging Mechanisms.
The Role of Mitochondrial Energy Metabolism in the Mechanism of Exercise Improving Depression.
Pharmacological effects, molecular mechanisms and strategies to improve bioavailability of curcumin in the treatment of neurodegenerative diseases.
Implications of mtDNA in human health and diseases.

Biomed Pharmacother. 2025 Jul 21. pii: S0753-3322(25)00557-8. [Epub ahead of print]190 118363

Biochanin A as a potential agent in the disease therapy via mitochondria-mediated mechanisms.

Meng-Ai Miao, Xiao-Qi Wu, Yuan Yuan, Ya-Jun Wang, Wen-Ting Dai.

  Biochanin A (BCA), a naturally occurring phytoestrogen, derived from plants such as Trifolium pratense L. (red clover), has attracted considerable interest due to its diverse pharmacological properties. As a dietary supplement, BCA is commonly utilized to alleviate symptoms associated with estrogen deficiency. Beyond its estrogenic effects, accumulating evidence highlights its broad-spectrum bioactivities, including anti-cancer, anti-diabetes, neuroprotection, anti-inflammation, antioxidant, organ protection, etc. Mitochondrial dysfunction is increasingly recognized as a central pathological mechanism underlying numerous diseases, making it a pivotal therapeutic target. Despite extensive research on BCA's pharmacological effects, a comprehensive review of its mitochondria-mediated mechanisms remains lacking. Here, on the basis of sufficient and comprehensive literature screening, we systematically review the extraordinary therapeutic potential of BCA in both in vitro and in vivo through its modulation of mitochondria-mediated pathways, including mitochondria-dependent apoptosis, reactive oxygen species (ROS) homeostasis, mitochondrial dynamics (fusion/fission), bioenergetics and mitochondrial biogenesis, as well as mitophagy. With this specific mechanism perspective, it helps us better understand the important role of mitochondria in the development of diseases and better target mitochondria to develop therapeutic regimens. Emerging studies highlight BCA's significant efficacy in mitigating disease progression, positioning it as a promising candidate for clinical translation and future drug development.

Keywords:  Biochanin A; Cancer; Metabolic diseases; Mitochondria-mediated mechanisms; Neurological disorders

DOI:  https://doi.org/10.1016/j.biopha.2025.118363
Mol Cell Biochem. 2025 Jul 24.

Sirtuins in mitophagy: key gatekeepers of mitochondrial quality.

Francisco Alejandro Lagunas-Rangel.

  Mitochondria are highly dynamic organelles essential for cellular energy production. However, they are also a primary source of reactive oxygen species, making them particularly vulnerable to oxidative damage. To preserve mitochondrial integrity, cells employ quality control mechanisms such as mitophagy, a selective form of autophagy that targets damaged or dysfunctional mitochondria for degradation. Among the key regulators of mitophagy are the sirtuins, a family of NAD+-dependent deacetylases. SIRT1, SIRT3, and SIRT6 generally promote mitophagy, whereas SIRT2, SIRT4, SIRT5, and SIRT7 often act as negative regulators. Sirtuin-mediated regulation of mitophagy is critical for maintaining cellular homeostasis and is implicated in a variety of physiological and pathological conditions. The aim of this review is to provide an overview focused on describing how sirtuins influence the mitophagy process. It highlights the different molecular mechanisms by which individual members of the sirtuin family modulate mitophagy, either by promoting or suppressing it, depending on the context. In addition, the review explores the relevance of sirtuin-regulated mitophagy in health and disease, emphasizing some conditions under which altered sirtuin activity could be harnessed for therapeutic benefit.

Keywords:  FOXO transcription factors; Mitochondria; PINK1-PARKIN pathway; Receptor-mediated mitophagy; Ubiquitin-mediated mitophagy

DOI:  https://doi.org/10.1007/s11010-025-05358-0
J Biol Chem. 2025 Jul 16. pii: S0021-9258(25)02333-6. [Epub ahead of print] 110483

Stressful situations: molecular insights on mitochondrial quality control pathways.

Sabrina Romanelli, Jean-François Trempe.

Mitochondrial quality control has emerged as an important area of research over the past decade, with more than 2,000 publications exploring the molecular pathways that regulate it. Mitochondria are essential for energy production and various cellular functions but are highly susceptible to damage from stressors such as protein misfolding, reactive oxygen species, and chemicals that disrupt the electron transport chain. If left unresolved, mitochondrial dysfunction can lead to health complications, including neurodegenerative disorders, cardiovascular diseases, and cancer. To maintain cellular health, cells evolved quality control pathways to remove damaged mitochondrial components. This review focuses on three key quality control responses: the PINK1-Parkin pathway, the DELE1-HRI pathway, and the mitochondrial unfolded protein response (UPRmt). While these pathways have distinct functions, there is ongoing debate about how they overlap and which responds first in different contexts. In this review, we discuss the physiological and structural mechanisms behind each pathway, explore how they interconnect, and highlight their differences and relevance to disease. By summarizing this information in a single review, we aim to enhance the molecular understanding of mitochondrial quality control, which can help highlight avenues for novel therapeutics for diseases associated to dysfunctional mitochondria.

DOI: https://doi.org/10.1016/j.jbc.2025.110483
J Adv Res. 2025 Jul 16. pii: S2090-1232(25)00546-6. [Epub ahead of print]

Mitochondrial cardiovascular diseases: molecular mechanisms, multi-omics exploration and therapeutic strategies.

Zhengyang Zhang, Xingwang Zhao, Xu Zhang, Sitong Wan, Peng An, Yinhua Zhu, Yongting Luo, Junjie Luo.

   BACKGROUND: Recent research highlights that abnormal mitochondrial function is a key feature in several cardiovascular diseases (CVDs), including aortic dissection, aortic aneurysm, atherosclerosis, pulmonary hypertension, and heart failure. We propose a novel concept termed mitochondrial cardiovascular diseases (Mito-CVDs) to define these conditions, which involve heart and vascular disorders directly driven by mitochondrial impairments, with the aim of highlighting the critical role of mitochondria in CVDs.
AIM OF REVIEW: This review aims to explore the complex relationship between mitochondrial impairments and Mito-CVDs, offering insights into potential molecular mechanisms and therapeutic strategies to address these diseases.
KEY SCIENTIFIC CONCEPTS OF REVIEW: The role of mitochondrial impairments in CVDs is expounded upon in detail, encompassing aspects such as excessive production of Reactive Oxygen Species (ROS), diminished Oxidative Phosphorylation (OXPHOS) capacity, and perturbations in Ca2+ transport. We also recapitulate the application of mitochondrial multi-omics, incorporating genomics, transcriptomics, proteomics, and metabolomics, within the realm of CVDs research. Additionally, single-cell mtDNA sequencing technology unfolds novel vistas for disclosing mitochondrial heterogeneity and status functional in Mito-CVDs. To enhance the understanding of Mito-CVDs, we present advanced diagnostic tools and categorize specific subtypes within each class of these disorders. Additionally, we propose Predictive, Preventive, and Personalized Medicine (PPPM) strategies designed to address mitochondrial impairments. Emerging therapeutic approaches are also discussed, including small-molecule modulators targeting key metabolic pathways, precision-based mtDNA editing technologies, and mitochondrial transplantation. A profound and exhaustive analysis of the mechanisms and therapeutic avenues associated with Mito-CVDs holds the potential to engender novel perspectives and opportunities for the prevention and treatment of CVDs.

Keywords:  Mito-CVDs; Mito-CVDs therapy; Mitochondrial impairment; Mitochondrial multi-omics; Predictive approach; Single-cell mtDNA sequencing; Treatments tailored to individualised patient profiles

DOI:  https://doi.org/10.1016/j.jare.2025.07.021
Biochim Biophys Acta Mol Basis Dis. 2025 Jul 17. pii: S0925-4439(25)00335-7. [Epub ahead of print]1871(8): 167987

Pharmacologic interventions targeting ovarian aging, cancer, and mitochondrial dysfunction: An updated evidence.

Alejandro Teppa-Garrán, Efraín Pérez-Peña, Luis Sobrevia, Reinaldo Marín.

  Ovarian aging is a major determinant of female reproductive longevity, characterized by declining oocyte quality and reduced ovarian reserve. With more women delaying childbearing, age-related infertility has become an urgent biomedical concern. Mitochondrial dysfunction plays a central role in this process, leading to oxidative damage and metabolic disturbances that impair oocyte competence. These alterations are linked to poorer outcomes in assisted reproductive technology (ART), particularly for women over 35, who face significantly reduced success rates. This review examines the key mechanisms of ovarian aging, including oxidative stress, DNA damage, telomere shortening, and mitochondrial dysfunction, all contributing to diminished oocyte quality and quantity. Special focus is given to sirtuins, especially SIRT1 and SIRT3, as critical regulators of redox balance in oocytes and granulosa cells. The review also addresses the impact of age-related changes on chromosomal cohesion and ovarian fibrosis. Importantly, mitochondrial insufficiency is increasingly recognized as a factor in broader age-related diseases, such as metabolic disorders and cancer, suggesting shared molecular pathways between reproductive aging and systemic health. Recent advances highlight the potential of targeted nutrient supplementation to modulate redox homeostasis, enhance sirtuin activity, and preserve mitochondrial function-strategies that may benefit both ovarian health and overall aging. This intersection of reproductive biology and mitochondrial medicine is driving interest in pharmacologic interventions to improve oocyte quality and mitigate age-related comorbidities.

Keywords:  Coenzyme Q10; DNA repair; Diabetes; Fertility; Mitochondrial dysfunction; Nicotinamide adenine dinucleotide; Ovarian aging; Oxidative stress; Sirtuins; cancer

DOI:  https://doi.org/10.1016/j.bbadis.2025.167987
Food Sci Nutr. 2025 Jul;13(7): e70661

Black Tea Aqueous Extract Extends Yeast Longevity via Antioxidant Gene Activation: Transcriptomic Analysis of Anti-Aging Mechanisms.

Jie Li, Qiyang Chen, Fuliang Xiao, Juan Yang, Sijia Zhou, Min Tang, Yujia Hou, Xiuming Zhai.

  Although tea polyphenols have antiaging potential, the molecular interplay between black tea components and cellular longevity remains unclear. This study has pioneered a dual approach combining Saccharomyces cerevisiae lifespan assays with comprehensive transcriptomics to dissect how black tea aqueous extract (BTAE) extends the chronological lifespan (CLS). Remarkably, BTAE induced a dose-dependent lifespan extension (34.6% maximum at 40 μg/mL), coupled with a 62% reduction in reactive oxygen species (ROS) accumulation and enhanced superoxide dismutase/catalase/ascorbate peroxidase (SOD/CAT/APX) enzyme activities-hallmarks of antioxidant system activation. Transcriptomic profiling revealed the action mechanism of BTAE: (1) upregulation of oxidative defense arsenals (SOD1/2, CTA1, and CTT1) and mitochondrial efficiency genes (COX10), and (2) strategic downregulation of apoptosis triggers (NMA111 and AIF1) and aging accelerators (MTH1 and HSPs). Additionally, we have identified novel targets including the OLE1-mediated membrane protection pathway and IRE1-dependent proteostatic regulation as key longevity switches. These findings establish BTAE as a multi-target anti-aging modulator and offer a roadmap for translating yeast discovery into mammalian aging interventions.

Keywords:  Saccharomyces cerevisiae; antioxidant capacity; anti‐aging; black tea; chronological lifespan

DOI:  https://doi.org/10.1002/fsn3.70661
Curr Issues Mol Biol. 2025 May 21. pii: 382. [Epub ahead of print]47(5):

The Role of Mitochondrial Energy Metabolism in the Mechanism of Exercise Improving Depression.

Yuwei Liu, Chenghao Zhong, Yuxin Yang, Jianbo Hu, Xiaoyan Yi, Jiating Huang, Haonan Li, Xiaojie Liu, Ke Xue, Xianghe Chen.

  Depression is the most disabling neuropsychiatric disorder, but its exact mechanisms remain unclear. Mitochondrial energy metabolism may play a key role in the onset and development of depression. Cytokines such as PGC-1α, NLRP3, and BDNF can influence mitochondrial energy metabolism by regulating mitochondrial biogenesis, immune inflammation, and neuroplasticity, thereby mediating the occurrence and progression of depression. Exercise can improve depression by regulating mitochondrial energy metabolism. The molecular mechanisms are closely related to the upregulation of exercise-induced PGC-1α, AMPK, SIRT1, and BDNF expression, as well as the downregulation of NLRP3 expression. These factors can activate key factors or pathways such as Nrf2, AMPK, and PKA/CREB, while inhibiting the excessive activation of NF-κB. Through these mechanisms, they regulate the expression of downstream target genes (such as TFAM, NRF1, CREB, and Bcl-2), thereby enhancing mitochondrial biogenesis and improving the quantity and quality of mitochondria. Additionally, they can act to inhibit the release of inflammatory factors to improve immune inflammation, enhance neuroplasticity, promote neuronal growth, and facilitate synapse formation and remodeling, thereby enhancing mitochondrial energy metabolism and improving its dysfunction, which in turn alleviates depression. Currently, there is a lack of systematic and comprehensive research on the mechanisms by which exercise improves depression through mitochondrial energy metabolism. Therefore, this article aims to review and analyze the role of mitochondrial energy metabolism in the improvement of depression through exercise, in order to provide a new theoretical basis and research ideas for the prevention and treatment of depression.

Keywords:  depression; energy metabolism; exercise; mitochondria; mitochondrial function

DOI:  https://doi.org/10.3390/cimb47050382
Front Pharmacol. 2025 ;16 1625821

Pharmacological effects, molecular mechanisms and strategies to improve bioavailability of curcumin in the treatment of neurodegenerative diseases.

Gang Wang, Xueyuan Zhou, Xiaoyan Pang, Ke Ma, Lu Li, Yuexin Song, Dongxia Hou, Xiaohua Wang.

  With the global population aging, the incidence of neurodegenerative diseases (NDs), such as Alzheimer's disease, Parkinson's disease, Huntington's disease and amyotrophic lateral sclerosis, has been progressively increasing. However, effective therapeutic strategies and clinical drugs for these disorders remain scarce. Curcumin, a natural polyphenolic compound primarily derived from the herbaceous plant Curcuma longa L., has been proposed as a promising candidate for ND treatment based on the excellent antioxidant, anti-inflammatory and neuroprotective properties. Its pharmacological activities encompass scavenging reactive oxygen species, mitigating toxic protein aggregation and cytotoxicity, repairing mitochondrial dysfunction, and inhibiting excessive neuronal apoptosis. Compared with synthetic drugs, curcumin demonstrates a more favorable safety profile with fewer side effects. Nevertheless, its clinical application is substantially hindered by poor bioavailability, which stems from low aqueous solubility, inefficient intestinal absorption, and rapid metabolism and systemic elimination. Conventional administration methods often fail to achieve effective concentrations in vivo. Further clinical trials are also required to validate the therapeutic efficacy and potential adverse effects in human subjects. This article systematically reviews the pathogenesis of NDs and the knowledge on curcumin including pharmacological effects, neuroprotective mechanisms, functions across specific NDs and advanced strategies to enhance the bioavailability, with the aim of promoting the development and clinical translation of curcumin-based therapeutics for NDs.

Keywords:  bioavailability; curcumin; natural medicine; neurodegenerative disease; pharmacological activity

DOI:  https://doi.org/10.3389/fphar.2025.1625821
BioTechnologia (Pozn). 2025 ;106(2): 209-222

Implications of mtDNA in human health and diseases.

Smruthi Seethashankar, Shruti Hariharan, Venkatachalam Deepa Parvathi.

  The maternally inherited autonomous organelles, mitochondria, are responsible for a myriad of functions within the cell. They may contain more than one copy of DNA and can themselves be present in multiple numbers within a cell. The integrity of the mitochondrial genome is affected by variations in DNA copy number or the presence of mutations. Compromising this integrity has been documented to result in disorders affecting various systems. Focusing on such trends could enhance knowledge essential for developing strategies to manage these disorders. Irregular patterns of mitochondrial DNA (mtDNA) copy number (CN) variation have been identified in various cancers. Reduced mtDNA CN has been associated with neurodegenerative disorders, cardiovascular diseases, and kidney disorders. Mutations in the mitochondrial respiratory chain complex have been linked to cardiomyopathy. High rates of mtDNA deletions have been found in aging patients and subjects with Parkinson's disease. While sperm function appears to deteriorate with increased mtDNA CN, oogenesis involves a significant increase to enable the oocyte to achieve fertilization and further development. Prospective therapies to treat mitochondrial diseases may include approaches that aim to reduce the levels of mutant mtDNA below the disease-causing threshold, such as targeted removal of defective mitochondria. Mutations in mitochondrial DNA contribute to various diseases; some single substitutions appear to disrupt the normalcy of more than one organ, underscoring the importance of mitochondrial genome integrity. The presence of mutations and copy number variations may serve as diagnostic markers and also provide insight into prognosis.

Keywords:  cancer; cardiovascular diseases; fertility; mitochondrial diseases; mtDNA; mtDNA CN; neurodegenerative diseases; renal diseases

DOI:  https://doi.org/10.5114/bta/204532