Lipid droplet biogenesis and functions in health and disease

Nature Reviews Endocrinology, Год журнала: 2023, Номер 19(8), С. 443 - 459

Опубликована: Май 23, 2023

Язык: Английский

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SGLT2 inhibitors: role in protective reprogramming of cardiac nutrient transport and metabolism

Nature Reviews Cardiology, Год журнала: 2023, Номер 20(7), С. 443 - 462

Опубликована: Янв. 6, 2023

Язык: Английский

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Mitochondrial signalling and homeostasis: from cell biology to neurological disease

Trends in Neurosciences, Год журнала: 2023, Номер 46(2), С. 137 - 152

Опубликована: Янв. 10, 2023

Efforts to understand how mitochondrial dysfunction contributes neurodegeneration have primarily focussed on the role of mitochondria in neuronal energy metabolism. However, progress understanding etiological nature emerging functions has yielded new ideas about basis neurological disease. Studies aimed at deciphering signal through interorganellar contacts, vesicular trafficking, and metabolic transmission revealed that regulation immunometabolism, cell death, organelle dynamics, neuroimmune interplay are critical determinants neural health. Moreover, homeostatic mechanisms exist protect health turnover via nanoscale proteostasis lysosomal degradation become integrated within signalling pathways support plasticity stress responses nervous system. This review highlights these distinct converge influence contribute disease pathology.

Язык: Английский

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Lipid droplets and polyunsaturated fatty acid trafficking: Balancing life and death

Frontiers in Cell and Developmental Biology, Год журнала: 2023, Номер 11

Опубликована: Янв. 27, 2023

Lipid droplets are fat storage organelles ubiquitously distributed across the eukaryotic kingdom. They have a central role in regulating lipid metabolism and undergo dynamic turnover of biogenesis breakdown to meet cellular requirements for fatty acids, including polyunsaturated acids. Polyunsaturated acids esterified membrane phospholipids define fluidity can be released by activity phospholipases A

Язык: Английский

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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

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Role of Perilipins in Oxidative Stress—Implications for Cardiovascular Disease

Antioxidants, Год журнала: 2024, Номер 13(2), С. 209 - 209

Опубликована: Фев. 7, 2024

Oxidative stress is the imbalance between production of reactive oxygen species (ROS) and antioxidants in a cell. In heart, oxidative may deteriorate calcium handling, cause arrhythmia, enhance maladaptive cardiac remodeling by induction hypertrophic apoptotic signaling pathways. Consequently, dysregulated ROS have been implicated numerous diseases, including heart failure, ischemia–reperfusion injury, hypertrophy, diabetic cardiomyopathy. Lipid droplets (LDs) are conserved intracellular organelles that enable safe stable storage neutral lipids within cytosol. LDs coated with proteins, perilipins (Plins) being one most abundant. this review, we will discuss interplay Plins. Indeed, Plins increasingly recognized for playing critical role beyond energy metabolism lipid handling. Numerous reports suggest an essential purpose LD biogenesis to alleviate cellular stress, such as stress. Given yet unmet suitability targets intervention cardiovascular disease, endogenous antioxidant capacity be beneficial.

Язык: Английский

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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

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DGAT1 activity synchronises with mitophagy to protect cells from metabolic rewiring by iron depletion

The EMBO Journal, Год журнала: 2022, Номер 41(10)

Опубликована: Апрель 12, 2022

Mitophagy removes defective mitochondria via lysosomal elimination. Increased mitophagy coincides with metabolic reprogramming, yet it remains unknown whether is a cause or consequence of such state changes. The signalling pathways that integrate to sustain cell and tissue integrity also remain poorly defined. We performed temporal metabolomics on mammalian cells treated deferiprone, therapeutic iron chelator stimulates PINK1/PARKIN-independent mitophagy. Iron depletion profoundly rewired the metabolome, hallmarked by remodelling lipid metabolism within minutes treatment. DGAT1-dependent droplet biosynthesis occurred several hours before mitochondrial clearance, droplets bordering upon chelation. demonstrate DGAT1 inhibition restricts in vitro, impaired homeostasis viability. Importantly, genetic vivo significantly neuronal locomotor function Drosophila. Our data define as potent signal rapidly reshapes establishes an unexpected synergy between safeguards integrity.

Язык: Английский

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BCAA metabolism in pancreatic cancer affects lipid balance by regulating fatty acid import into mitochondria

Cancer & Metabolism, Год журнала: 2024, Номер 12(1)

Опубликована: Март 26, 2024

Abstract Background Pancreatic ductal adenocarcinoma (PDAC) has been associated with the host dysmetabolism of branched-chain amino acids (BCAAs), however, implications for role BCAA metabolism in PDAC development or progression are not clear. The mitochondrial catabolism valine, leucine, and isoleucine is a multistep process leading to production short-chain R-CoA species. They can be subsequently exported from mitochondria as carnitines (SC-CARs), utilized anabolic pathways, released cells. Methods We examined specificities cellular adaptation strategies starvation cells vitro. used metabolomics lipidomics quantify major metabolic changes response withdrawal. Using confocal microscopy flow cytometry we quantified fluorescence BODIPY probe level lipid droplets (LDs). BODIPY-conjugated palmitate evaluate transport fatty (FAs) into mitochondria. Also, have developed protocol quantification SC-CARs, BCAA-derived metabolites. Results profiling, found that leads massive triglyceride (TG) synthesis LD accumulation. This was suppression activated FA matrix. import rescued inhibitor acetyl-CoA carboxylase (ACC) activator AMP kinase (AMPK), which both regulate carnitine palmitoyltransferase 1A (CPT1) activation status. Conclusions Our data suggest required long chain (LC-CARs) mitochondria, whereas disruption this link results redirection FAs TG its deposition LDs. propose mechanism protects against overload LC-CARs it might part universal reaction acid perturbations during cancer growth, regulating handling storage.

Язык: Английский

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Longitudinal autophagy profiling of the mammalian brain reveals sustained mitophagy throughout healthy aging

The EMBO Journal, Год журнала: 2024, Номер unknown

Опубликована: Окт. 4, 2024

Abstract Mitophagy neutralizes mitochondrial damage, thereby preventing cellular dysfunction and apoptosis. Defects in mitophagy have been strongly implicated age-related neurodegenerative disorders such as Parkinson’s Alzheimer’s disease. While decreases throughout the lifespan of short-lived model organisms, it remains unknown whether a decline occurs aging mammalian brain—a question fundamental importance for understanding cell type- region-specific susceptibility to neurodegeneration. Here, we define longitudinal dynamics basal macroautophagy across neuronal non-neuronal types within intact mouse brain vivo. Quantitative profiling reporter cohorts from young geriatric ages reveals cell- tissue-specific alterations between distinct subregions populations, including dopaminergic neurons, cerebellar Purkinje cells, astrocytes, microglia interneurons. We also find that healthy is hallmarked by dynamic accumulation differentially acidified lysosomes several neural subsets. Our findings argue against any widespread mitophagic activity, instead demonstrating fluctuations trajectory, with strong implications ongoing theragnostic development.

Язык: Английский

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