Mitochondrial ROS, a trigger for mitochondrial dysfunction and inflammasome activation and a therapeutic target in liver diseases DOI Creative Commons

Hala Saeed Jaara,

Sandra Torres

Published: Dec. 10, 2024

Mitochondria are essential organelles responsible for intracellular energy production and play crucial roles in cellular metabolism, inflammation, apoptosis. Reactive oxygen species (ROS) primarily produced the mitochondria endoplasmic reticulum of hepatocytes due to activity cytochrome P450 enzymes. Under ideal conditions, cells have specific molecular mechanisms that manage oxidative stress levels, thus ensuring a balance between oxidants antioxidants. The interplay ROS-induced mitochondrial dysfunction activation NLRP3 (nucleotide-binding oligomerization domain-like receptor family, pyrin domain containing 3) inflammasome context liver diseases has been extensively studied. However, exact by which promote contribute onset disease remain unclear. This review aims elucidate recently discovered regulation disorders, including alcohol-related (ALD), metabolic-associated steatotic (MASLD), hepatocellular carcinoma (HCC). Finally, it summarizes various natural pharmaceutical agents can mitigate damage modulating through pathways. work serves as an important resource identifying new therapeutic approaches provides further support advancing understanding diseases.

Language: Английский

Deciphering the Power of Resveratrol in Mitophagy: From Molecular Mechanisms to Therapeutic Applications DOI Open Access
Hongmei Liu, Yixuan Song, Huan Wang

et al.

Phytotherapy Research, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 4, 2025

Resveratrol (RES), a natural polyphenolic compound, has garnered significant attention for its therapeutic potential in various pathological conditions. This review explores how RES modulates mitophagy-the selective autophagic degradation of mitochondria essential maintaining cellular homeostasis. promotes the initiation and execution mitophagy by enhancing PINK1/Parkin-mediated mitochondrial clearance, reducing reactive oxygen species production, mitigating apoptosis, thereby preserving integrity. Additionally, regulates through activation key molecular targets such as AMP-activated protein kinase (AMPK), mechanistic target rapamycin (mTOR), deacetylases (SIRT1 SIRT3), quality control (MQC) pathways, demonstrating substantial effects multiple disease models. We provide detailed account biosynthetic pharmacokinetics, metabolic characteristics RES, focusing on role modulation implications medical applications. Potential adverse associated with clinical use are also discussed. Despite promising properties, application is limited issues bioavailability pharmacokinetic profiles. Future research should concentrate developing derivatives that precisely modulate mitophagy, unlocking new avenues therapy.

Language: Английский

Citations

3
Aging, cancer, and autophagy: connections and therapeutic perspectives DOI Creative Commons

Begoña Zapatería,

Esperanza Arias

Frontiers in Molecular Biosciences, Journal Year: 2025, Volume and Issue: 11

Published: Jan. 28, 2025

Aging and cancer are intricately linked through shared molecular processes that influence both the onset of malignancy progression age-related decline. As organisms age, cellular stress, genomic instability, an accumulation senescent cells create a pro-inflammatory environment conducive to development. Autophagy, process responsible for degrading recycling damaged components, plays pivotal role in this relationship. While autophagy acts as tumor-suppressive mechanism by preventing organelles proteins, often exploit it survive under conditions metabolic stress treatment resistance. The interplay between aging, cancer, reveals key insights into tumorigenesis, senescence, proteostasis dysfunction. This review explores connections these processes, emphasizing potential autophagy-targeted therapies strategies could be further explored aging treatment. Understanding dual roles suppressing promoting offers promising avenues therapeutic interventions aimed at improving outcomes elderly patients while addressing deterioration.

Language: Английский

Citations

2
Editorial: Lipids and membrane contacts – structure, functional aspects and implications on ageing, cell death and autophagy, volume II DOI Creative Commons
Christopher Beh,

Alexandre Toulmay,

Patrick Rockenfeller

et al.

Frontiers in Cell and Developmental Biology, Journal Year: 2025, Volume and Issue: 13

Published: March 19, 2025

MCSs act as membrane connectors, establishing intracellular highways for lipid traWicking while also functioning hubs inter-compartment communication and coordinating stress responses (Rockenfeller Gourlay, 2018;Prinz et al., 2020;Zaman 2020). They play multiple roles in regulating metazoan calcium signaling (Ke 2025;Stefan, Less appreciated, however, are crucial the de novo biogenesis of some compartments, such autophagosomes, which depend on contacts with ER mitochondria assembly (Herrera-Cruz Simmen, 2017;Metur Klionsky, 2020;Molino 2017;Gómez-Sánchez 2018;Valverde 2019;Zwilling Reggiori, 2022). Beyond autophagosome biogenesis, autophagy-related direct selective organelle degradation, including mitochondrial autophagy or mitophagy (Kohler 2020;Zwilling 2022).MCSs regulate balance and, through mitophagy, remove damaged to maintain a stable population that meets cellular demands (Schrader 2015). MERCs (Mitochondria -ER contact sites) initiate degradation (Yang As MERC-interacting protein, FUNDC1 (FUN14 Domain Containing 1) is key regulator engulfment during mitophagy. an integral outer-membrane protein containing specific domain interaction LC3, mammalian homologue Atg8 regulates formation (Liu 2012;Lee 2025). The dynamics this particularly important hypoxic cells where accumulates at MAMs then binds LC3 recruit autophagosomes 2012;Wu 2016). role mediating hypoxia induced has been established heart injury, it promising target treating tumours other human disorders (Zhang 2016;Tan 2022;Atici 2023;Dong Zhang, 2024). In context, Li colleagues contribute special issue their review article "Multiple receptor events kidney disease," focusing renal disease (Li authors explore mechanisms by context diseases aWect kidney, metabolic organ.Kumar Research Topic comprehensive review, "The evolving landscape ER-LD sites," they droplet (LD) (Kumar describe unique bridge LD monolayer bilayer discuss within ER, well maintaining cytoplasmic LDs ER/lipid homeostasis. highlight importance Seipin, yeast Sei1/Fld1, defining sites occurs maintenance. covers current insights into molecular tethers forming interfaces, study complements articles first volume research topic, detailed several diWerent compartments.In "Imaging proteomics toolkits studying sites" Gamuyao Chang present technical advances analyzing tethering complexes (Gamuyao Chang, 2024), further expanding scope collection reviews. genetic approaches functional analysis MCSs, work focuses imaging techniques using MCS reporters proximity labeling profile complexes. It discusses challenges unbiased identification associated components.The extended synaptotagmin cancer research" Pan al. explores how influence progression changes might be utilized diagnostic biomarker (Pan 2023). focus synaptotagmins (E-Syts) signaling, linking them tumor proliferation, progression, metastasis, apoptosis, drug resistance, treatment. By highlighting E-Syts integrating both pathways, uses starting point direction understanding cancer.This second addresses original questions we raised about confronting However, remain regarding pathways contribution pathology, these will continue drive new discovered. With additional complexes, future likely response metabolic, developmental, programs. Perhaps studies lay groundwork yet another topic regulation.

Language: Английский

Citations

0
PSMA2 promotes chemo- and radioresistance of oral squamous cell carcinoma by modulating mitophagy pathway DOI Creative Commons
Chun‐I Wang, Cheng‐Yi Chen, Ting-Wen Chen

et al.

Cell Death Discovery, Journal Year: 2025, Volume and Issue: 11(1)

Published: Jan. 10, 2025

Abstract Oral cavity squamous cell carcinoma (OSCC) represents the most prevalent malignancy among head and neck carcinomas (HNSCCs). Standard treatment modalities include surgical resection combined with radiation chemotherapy. However, locoregional failure remains a critical issue affecting prognosis of OSCC patients, largely due to tumor resistance against or In this study, we established gene database related recurrence identified PSMA2 as novel molecule influencing in patients. An independent Taiwanese cohort confirmed that elevated transcript levels were associated poorer contributed chemo- radioresistance phenotype OSCC. Furthermore, regulates cycle, mitochondrial dysfunction, mitophagy, thereby contributing carcinogenesis resistance. Notably, mitophagy inducer exhibit antitumor effects PSMA2-overexpressing xenograft mouse model. Collectively, our results provide mechanistic understanding atypical function promoting recurrence.

Language: Английский

Citations

0
The potential of natural herbal plants in the treatment and prevention of non-small cell lung cancer: An encounter between ferroptosis and mitophagy DOI
Yujie Yang,

Bing Jiang,

Lijuan Shi

et al.

Journal of Ethnopharmacology, Journal Year: 2025, Volume and Issue: unknown, P. 119555 - 119555

Published: Feb. 1, 2025

Language: Английский

Citations

0
Galectin-8 drives ERK-dependent mitochondrial fragmentation, perinuclear relocation and mitophagy, with metabolic adaptations for cell proliferation DOI Creative Commons
Adely de la Peña, Cláudio Retamal,

Francisca Pérez-Molina

et al.

European Journal of Cell Biology, Journal Year: 2025, Volume and Issue: unknown, P. 151488 - 151488

Published: April 1, 2025

Mitochondria adapt to the cell proliferative demands induced by growth factors through dynamic changes in morphology, distribution, and metabolic activity. Galectin-8 (Gal-8), a carbohydrate-binding protein that promotes proliferation transactivating EGFR-ERK signaling pathway, is overexpressed several cancers. However, its impact on mitochondrial dynamics during remains unknown. Using MDCK RPTEC kidney epithelial cells, we demonstrate Gal-8 induces fragmentation perinuclear redistribution. Additionally, mitochondria adopt donut-shaped morphologies, live-cell imaging with two Keima-based reporters demonstrates Gal-8-induced mitophagy. ERK inhibition abrogates all these proliferation. Studies established mutant versions of CHO cells reveal response require interactions between N-terminal carbohydrate recognition domain α-2,3-sialylated N-glycans at surface. DRP1, key regulator fission, becomes phosphorylated or an ERK-dependent manner, mediating Bafilomycin A proliferation, suggesting mitophagy serves as adaptation demands. Functional analysis under stimulation shows maintain active electron transport chain, partially uncoupled from ATP synthesis, increased membrane potential, indicative healthy mitochondria. Meanwhile, exhibit extracellular acidification rate lactate production via aerobic glycolysis, hallmark state. Our findings integrate adaptations potential implications for physiology, disease, therapeutic strategies.

Language: Английский

Citations

0
Mitochondrial quality control in hematopoietic stem cells: mechanisms, implications, and therapeutic opportunities DOI Creative Commons

Yun Liao,

Stacia Octaviani,

Zhen Tian

et al.

Stem Cell Research & Therapy, Journal Year: 2025, Volume and Issue: 16(1)

Published: April 15, 2025

Mitochondrial quality control (MQC) is a critical mechanism for maintaining mitochondrial function and cellular metabolic homeostasis, playing an essential role in the self-renewal, differentiation, long-term stability of hematopoietic stem cells (HSCs). Recent research highlights central importance MQC HSC biology, particularly roles mitophagy, biogenesis, fission, fusion transfer regulating function. Mitophagy ensures removal damaged mitochondria, low levels reactive oxygen species (ROS) HSCs, thereby preventing premature aging functional decline. Concurrently, biogenesis adjusts key regulators such as transcription factor A (TFAM) peroxisome proliferator-activated receptor-γ coactivator 1α (PGC-1α) to meet environmental demands, ensuring needs HSCs are met. Additionally, transfer, form intercellular material exchange, facilitates mitochondria from bone marrow stromal contributing damage repair support. Although existing studies have revealed significance function, precise molecular mechanisms interactions among different regulatory pathways remain be fully elucidated. Furthermore, potential dysfunction disorders, including its involvement disease progression therapeutic resistance, not yet understood. This review discusses functions under physiological pathological conditions, applications. By summarizing current progress this field, we aim provide insights further development innovative treatment strategies.

Language: Английский

Citations

0
Mitophagy in Doxorubicin-Induced Cardiotoxicity: Insights into Molecular Biology and Novel Therapeutic Strategies DOI Creative Commons
Heng Zhang, Saiyang Xie, Wei Deng

et al.

Biomolecules, Journal Year: 2024, Volume and Issue: 14(12), P. 1614 - 1614

Published: Dec. 17, 2024

Doxorubicin is a chemotherapeutic drug utilized for solid tumors and hematologic malignancies, but its clinical application hampered by life-threatening cardiotoxicity, including cardiac dilation heart failure. Mitophagy, cargo-specific form of autophagy, specifically used to eliminate damaged mitochondria in autophagosomes through hydrolytic degradation following fusion with lysosomes. Recent advances have unveiled major role defective mitophagy the etiology DOX-induced cardiotoxicity. Moreover, specific interventions targeting this mechanism preserve mitochondrial function emerged as potential therapeutic strategies attenuate However, translation challenging because unclear mechanisms action pharmacological adverse effects. This review aims offer fresh perspectives on development cardiotoxicity investigate that focus improve management.

Language: Английский

Citations

1
Mitochondrial ROS, a trigger for mitochondrial dysfunction and inflammasome activation and a therapeutic target in liver diseases DOI Creative Commons

Hala Saeed Jaara,

Sandra Torres

Published: Dec. 10, 2024

Mitochondria are essential organelles responsible for intracellular energy production and play crucial roles in cellular metabolism, inflammation, apoptosis. Reactive oxygen species (ROS) primarily produced the mitochondria endoplasmic reticulum of hepatocytes due to activity cytochrome P450 enzymes. Under ideal conditions, cells have specific molecular mechanisms that manage oxidative stress levels, thus ensuring a balance between oxidants antioxidants. The interplay ROS-induced mitochondrial dysfunction activation NLRP3 (nucleotide-binding oligomerization domain-like receptor family, pyrin domain containing 3) inflammasome context liver diseases has been extensively studied. However, exact by which promote contribute onset disease remain unclear. This review aims elucidate recently discovered regulation disorders, including alcohol-related (ALD), metabolic-associated steatotic (MASLD), hepatocellular carcinoma (HCC). Finally, it summarizes various natural pharmaceutical agents can mitigate damage modulating through pathways. work serves as an important resource identifying new therapeutic approaches provides further support advancing understanding diseases.

Language: Английский

Citations

0