Lipid Droplet–Mitochondria Contacts in Health and Disease

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(13), P. 6878 - 6878

Published: June 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

Language: Английский

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Iron depletion has different consequences on the growth and survival of Toxoplasma gondii strains

Virulence, Journal Year: 2024, Volume and Issue: 15(1)

Published: March 20, 2024

Toxoplasma gondii is an obligate intracellular parasite responsible for a pathology called toxoplasmosis, which primarily affects immunocompromised individuals and developing foetuses. The can scavenge essential nutrients from its host to support growth survival. Among them, iron one of the most important elements needed sustain basic cellular functions as it involved in number key metabolic processes, including oxygen transport, redox balance, electron transport. We evaluated effects chelator on development several strains found that they differed their ability tolerate depletion. parasites usually associated with model acute toxoplasmosis was strongly affected by depletion, whereas cystogenic were less sensitive able convert into persisting developmental forms are chronic form disease. Ultrastructural biochemical characterization impact depletion also highlighted striking changes both metabolism host, marked accumulation lipid droplets perturbation homoeostasis. Overall, our study demonstrates although has effect T. gondii, more profound actively dividing parasites, metabolically active may be avoid some detrimental consequences.

Language: Английский

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An AI-guided screen identifies probucol as an enhancer of mitophagy through modulation of lipid droplets

PLoS Biology, Journal Year: 2023, Volume and Issue: 21(3), P. e3001977 - e3001977

Published: March 2, 2023

Failures in mitophagy, a process by which damaged mitochondria are cleared, results neurodegeneration, while enhancing mitophagy promotes the survival of dopaminergic neurons. Using an artificial intelligence platform, we employed natural language processing approach to evaluate semantic similarity candidate molecules set well-established enhancers. Top candidates were screened cell-based mitochondrial clearance assay. Probucol, lipid-lowering drug, was validated across several orthogonal assays. In vivo, probucol improved survival, locomotor function, and neuron loss zebrafish fly models damage. Probucol functioned independently PINK1/Parkin, but its effects on vivo depended ABCA1, negatively regulated following Autophagosome lysosomal markers elevated treatment addition increased contact between lipid droplets (LDs) mitochondria. Conversely, LD expansion, occurs damage, suppressed probucol-mediated enhancement required LDs. Probucol-mediated dynamics changes may prime cell for more efficient mitophagic response

Language: Английский

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Tools to Dissect Lipid Droplet Regulation, Players, and Mechanisms

ACS Chemical Biology, Journal Year: 2025, Volume and Issue: unknown

Published: March 4, 2025

Spurred by the authors' own recent discovery of reactive metabolite-regulated nexuses involving lipid droplets (LDs), this perspective discusses latest knowledge and multifaceted approaches toward deconstructing function these dynamic organelles, LD-associated localized signaling networks, protein players. Despite accumulating surrounding families pathways conserved importance for LD homeostasis surveillance maintenance across taxa, much remains to be understood at molecular level. In particular, metabolic stress-triggered contextual changes in LD-proteins' functions, crosstalk with other feedback loops how are specifically rewired disease states remain illuminated spatiotemporal precision. We hope promotes an increased interest essential organelles innovations new tools strategies better understand context-specific regulation critical organismal health.

Language: Английский

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Comparison of Effects of Iron and Multiple Micronutrient Supplementation on Hematological and Growth Indicators among Older Children, Adolescents, and Young Adults in Low- and Middle-Income Countries: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Nutrition Reviews, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 4, 2025

Middle childhood, adolescence, and young adulthood are characterized by high nutritional demands vulnerability to anemia. Limited efforts have been made synthesize the evidence comparing effects of iron multiple micronutrient (MMN) supplementation in these populations. In this study we sought examine MMN on anemia anthropometric variables among people aged 5 24 years low- middle-income countries. The PubMed, Embase, Cochrane Library, CINAHL databases were searched from inception July 2024 identify 50 randomized controlled trials (RCTs) or with outcomes. Only RCTs that used included analysis. Compared placebo, was associated 5.81 g/L (95% CI: 4.19-7.44 g/L) 4.82 2.32-7.32 incremental increases hemoglobin levels, respectively. therapeutic (hemoglobin: 9.3 g/L, 95% 1.52-17.09 (10.24 5.10-15.39 both observed populations older children, adolescents, adults Stratified analysis showed either supplementation, higher content (> 30 mg/d) could lead a increment hemoglobin, while shorter intervention duration (< 3 months) more benefits improving hemoglobin. For ferritin, significant benefit only not MMN. Iron also found decrease serum transferrin receptor zinc protoporphyrin, but there no effect C-reactive protein. growth indicators, increase weight (0.52 kg, 0.12-0.93 kg), height (0.87 cm, 0.16-1.59 cm). Overall, compared had similarly beneficial level adults, some indication may be differential indicators.

Language: Английский

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Mitophagy in the aging nervous system

Frontiers in Cell and Developmental Biology, Journal Year: 2022, Volume and Issue: 10

Published: Oct. 11, 2022

Aging is characterised by the progressive accumulation of cellular dysfunction, stress, and inflammation. A large body evidence implicates mitochondrial dysfunction as a cause or consequence age-related diseases including metabolic disorders, neuropathies, various forms cancer neurodegenerative diseases. Because neurons have high demands cannot divide, they are especially vulnerable to which promotes cell cytotoxicity. Mitophagy neutralises providing an adaptive quality control strategy that sustains homeostasis. has been extensively studied inducible stress response in cultured cells short-lived model organisms. In contrast, our understanding physiological mitophagy mammalian aging remains extremely limited, particularly nervous system. The recent profiling reporter mice revealed variegated vistas steady-state destruction across different tissues. discovery patients with congenital autophagy deficiency provokes further intrigue into mechanisms underpin neural integrity. These dimensions considerable implications for targeting other degradative pathways neurological disease.

Language: Английский

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Lipid Droplet in Lipodystrophy and Neurodegeneration

Biology of the Cell, Journal Year: 2025, Volume and Issue: 117(4)

Published: April 1, 2025

ABSTRACT Lipid droplets are ubiquitous yet distinct intracellular organelles that gaining attention for their uses outside of energy storage. Their formation, role in the physiological function, and onset pathology have been recently. structure, synthesis, turnover play dynamic roles both lipodystrophy neurodegeneration. Factors like development, aging, inflammation, cellular stress regulate synthesis lipid droplets. The biogenesis has a critical reducing stress. droplets, response to stress, sequester hazardous lipids into neutral core, preserving redox balance while guarding against lipotoxicity. Thus, maintenance droplet homeostasis adipose tissue, CNS, other body tissues is essential maintaining organismal health. Insulin resistance, hypertriglyceridemia, accumulation severe metabolic abnormalities accompany lipodystrophy‐related fat deficit. Accumulation detected almost all neurodegenerative diseases Alzheimer's, Parkinson's, Huntington's, Hereditary spastic paraplegia. Hence, regulation can be used as an alternative approach treatment several diseases. current review summarizes composition, biogenesis, with emphasis on factors responsible importance disease.

Language: Английский

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Lipid droplets promote efficient mitophagy

Autophagy, Journal Year: 2022, Volume and Issue: 19(2), P. 724 - 725

Published: Aug. 8, 2022

Mitophagy neutralizes defective mitochondria via lysosomal elimination. Increased levels of mitophagy hallmark metabolic transitions and are induced by iron depletion, yet its basis has not been studied in-depth. How integrates with different homeostatic mechanisms to support integrity is incompletely understood. We examined adaptations in cells treated deferiprone (DFP), a therapeutic chelator known induce PINK1-PRKN-independent mitophagy. found that depletion profoundly rewired the cellular metabolome, remodeling lipid metabolism within minutes treatment. DGAT1-dependent droplet biosynthesis occurs upstream mitochondrial turnover, many LDs bordering upon chelation. Surprisingly, DGAT1 inhibition restricts vitro dysfunction. Genetic mdy/DGAT1 vivo impairs neuronal locomotor function Drosophila, demonstrating physiological relevance our findings.

Language: Английский

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GoatFADS2controlling fatty acid metabolism is directly regulated bySREBP1in mammary epithelial cells

Journal of Animal Science, Journal Year: 2023, Volume and Issue: 101

Published: Jan. 1, 2023

Abstract Goat milk provides benefits to human health due its richness in bioactive components, such as polyunsaturated fatty acids (PUFAs). The acid desaturase 2 (FADS2) is the first rate-limiting enzyme PUFAs biosynthesis. However, role and transcriptional regulation mechanisms metabolism dairy goat remain unclear. Here, our study revealed that FADS2 gene was highly expressed during peak lactation compared with dry period, early lactation, late lactation. content of triacylglycerol (TAG) enhanced increasing mRNA expression TAG synthesis genes (diacylglycerol acyltransferase 1/2, DGAT1/2) FADS2-overexpressed mammary epithelial cells (GMECs). Overexpression positively correlated elevated concentrations dihomo-gamma-linolenic (DGLA) docosahexaenoic (DHA) GMECs. BODIPY staining showed promoted lipid droplet accumulation To clarify regulatory FADS2, 2,226 bp length promoter obtained. Deletion mutation assays core region located between −375 −26 region, which contained SRE1 (−361/−351) SRE2 (−191/−181) cis-acting elements transcription factor sterol element-binding protein 1 (SREBP1). SREBP1 relative luciferase activity single mutant or SRE2, vice versa, failed alter joint SRE2. Chromatin immunoprecipitation (ChIP) site-directed further demonstrated regulated by binding SRE sites vivo vitro. In addition, levels were significantly decreased targeting genome via CRISPR interference (CRISPRi) system. These findings establish a direct for regulating goat, providing new insights into gland ruminants.

Language: Английский

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Fast and quantitative mitophagy assessment by flow cytometry using the mito-QC reporter

Frontiers in Cell and Developmental Biology, Journal Year: 2024, Volume and Issue: 12

Published: Sept. 11, 2024

Mitochondrial quality control is finely tuned by mitophagy, the selective degradation of mitochondria through autophagy, and mitochondrial biogenesis. Removal damaged essential to preserve cellular bioenergetics prevent detrimental events such as sustained mitoROS production, pro-apoptotic cytochrome c release or mtDNA leakage. The array tools available study mitophagy very limited but in constant development. Almost a decade ago, we developed method assess flux using MitoTracker Deep Red combination with lysosomal inhibitors. Now, novel tandem-fluorescence reporter

Language: Английский

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