New insights into the role of mitochondrial dynamics in oxidative stress-induced diseases

Biomedicine & Pharmacotherapy, Год журнала: 2024, Номер 178, С. 117084 - 117084

Опубликована: Авг. 1, 2024

The accumulation of excess reactive oxygen species (ROS) can lead to oxidative stress (OS), which induce gene mutations, protein denaturation, and lipid peroxidation directly or indirectly. expression is reduced ATP level in cells, increased cytoplasmic Ca

Язык: Английский

---

ATG14 targets lipid droplets and acts as an autophagic receptor for syntaxin18-regulated lipid droplet turnover

Nature Communications, Год журнала: 2024, Номер 15(1)

Опубликована: Янв. 20, 2024

Язык: Английский

---

Dual modes of DNA N ⁶ -methyladenine maintenance by distinct methyltransferase complexes

Proceedings of the National Academy of Sciences, Год журнала: 2025, Номер 122(3)

Опубликована: Янв. 15, 2025

Stable inheritance of DNA N 6 -methyladenine (6mA) is crucial for its biological functions in eukaryotes. Here, we identify two distinct methyltransferase (MTase) complexes, both sharing the catalytic subunit AMT1, but featuring AMT6 and AMT7 as their unique components, respectively. While complexes are jointly responsible 6mA maintenance methylation, they exhibit enzymology, DNA/chromatin affinity, genomic distribution, knockout phenotypes. complex, high MTase activity processivity, connected to transcription-associated epigenetic marks, including H2A.Z H3K4me3, required bulk methylation. In contrast, with reduced recruited by PCNA initiate methylation immediately after replication. These coordinate By integrating signals from replication transcription, this mechanism ensures faithful efficient transmission an mark

Язык: Английский

---

Coronaviral ORF6 protein mediates inter‐organelle contacts and modulates host cell lipid flux for virus production

The EMBO Journal, Год журнала: 2023, Номер 42(13)

Опубликована: Май 23, 2023

Abstract Lipid droplets (LDs) form inter‐organelle contacts with the endoplasmic reticulum (ER) that promote their biogenesis, while LD mitochondria enhance β‐oxidation of contained fatty acids. Viruses have been shown to take advantage lipid viral production, but it remains unclear whether they also modulate interactions between LDs and other organelles. Here, we showed coronavirus ORF6 protein targets is localized mitochondria‐LD ER‐LD contact sites, where regulates biogenesis lipolysis. At molecular level, find inserts into monolayer via its two amphipathic helices. further interacts ER membrane proteins BAP31 USE1 mediate ER‐LDs formation. Additionally, SAM complex in mitochondrial outer link LDs. In doing so, promotes cellular lipolysis reprogram host cell flux facilitate production.

Язык: Английский

---

Functional interplay of lipid droplets and mitochondria

FEBS Letters, Год журнала: 2024, Номер 598(10), С. 1235 - 1251

Опубликована: Янв. 24, 2024

Our body stores energy mostly in form of fatty acids (FAs) lipid droplets (LDs). From there the FAs can be mobilized and transferred to peroxisomes mitochondria. This transfer is dependent on close opposition LDs mitochondria happens at membrane contact sites. However, composition dynamics these sites not well understood, which part due dependence metabolic state cell cell- tissue-type. Here, we summarize current knowledge contacts between both mammals yeast Saccharomyces cerevisiae, various are studied. We discuss possible functions site their implication disease.

Язык: Английский

---

Lipid Droplet–Mitochondria Contacts in Health and Disease

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(13), С. 6878 - 6878

Опубликована: Июнь 22, 2024

The orchestration of cellular metabolism and redox balance is a complex, multifaceted process crucial for maintaining homeostasis. Lipid droplets (LDs), once considered inert storage depots neutral lipids, are now recognized as dynamic organelles critical in lipid energy regulation. Mitochondria, the powerhouses cell, play central role production, metabolic pathways, signaling. physical functional contacts between LDs mitochondria facilitate direct transfer primarily fatty acids, which mitochondrial β-oxidation, thus influencing homeostasis health. This review highlights recent advances understanding mechanisms governing LD-mitochondria interactions their regulation, drawing attention to proteins pathways that mediate these contacts. We discuss physiological relevance interactions, emphasizing within cells, how processes response demands stress conditions. Furthermore, we explore pathological implications dysregulated particularly context diseases such obesity, diabetes, non-alcoholic liver disease, potential links cardiovascular neurodegenerative diseases. Conclusively, this provides comprehensive overview current underscoring significance suggesting future research directions could unveil novel therapeutic targets degenerative

Язык: Английский

---

Evasion of NKG2D-mediated cytotoxic immunity by sarbecoviruses

Cell, Год журнала: 2024, Номер 187(10), С. 2393 - 2410.e14

Опубликована: Апрель 22, 2024

Язык: Английский

---

A Membrane‐Targeting Aggregation‐Induced Emission Probe for Monitoring Lipid Droplet Dynamics in Ischemia/Reperfusion‐Induced Cardiomyocyte Ferroptosis

Advanced Science, Год журнала: 2024, Номер 11(26)

Опубликована: Май 2, 2024

Myocardial ischemia/reperfusion injury (MIRI) is the leading cause of irreversible myocardial damage. A pivotal pathogenic factor (I/R)-induced cardiomyocyte ferroptosis, marked by iron overload and lipid peroxidation. However, impact droplet (LD) changes on I/R-induced ferroptosis unclear. In this study, an aggregation-induced emission probe, TPABTBP developed that used for imaging dynamic in LD during ferroptosis. exhibits excellent LD-specificity, superior capability monitoring lipophagy, remarkable photostability. Molecular dynamics (MD) simulation super-resolution fluorescence demonstrate specifically localized to phospholipid monolayer membrane LDs. Imaging LDs cardiomyocytes tissue model mice with MIRI reveals accumulation level increase early reperfusion stage (0-9 h) but decrease late (>24 via lipophagy. The inhibition breakdown significantly reduces peroxidation cardiomyocytes. Furthermore, it demonstrated chloroquine (CQ), FDA-approved autophagy modulator, can inhibit thereby attenuating mice. This study describes ischemia suggests a potential therapeutic target intervention.

Язык: Английский

---

Mitochondria–membranous organelle contacts at a glance

Journal of Cell Science, Год журнала: 2025, Номер 138(9)

Опубликована: Май 1, 2025

ABSTRACT Mitochondrial contact sites are specialized interfaces where mitochondria physically interact with other organelles. Stabilized by molecular tethers and defined unique proteomic lipidomic profiles, these enable direct interorganellar communication functional coordination, playing crucial roles in cellular physiology homeostasis. Recent advances have expanded our knowledge of site-resident proteins, illuminated the dynamic adaptive nature interfaces, clarified their contribution to pathophysiology. In this Cell Science at a Glance article accompanying poster, we summarize mitochondrial contacts that been characterized mammals, mechanisms underlying formation, principal functions.

Язык: Английский

---

Lipid Droplets in Virus Replication

FEBS Letters, Год журнала: 2024, Номер 598(10), С. 1299 - 1300

Опубликована: Фев. 13, 2024

Intracellular pathogens rely on host metabolic networks for multiplication. Enveloped viruses need lipids formation of the viral envelope and positive sense RNA that replicate in membranous inclusions require replication compartments. In addition, all intracellular energy their replicative cycle. As triglycerides lipid droplets are main storage unit cells major source membrane lipids, it is not surprising have evolved various strategies to exploit different aspects droplet biology.

Язык: Английский

---