Spatially resolved rewiring of mitochondria-lipid droplet interactions in hepatic lipid homeostasis DOI Creative Commons
Sun Woo Sophie Kang,

Lauryn A. Brown,

Colin B. Miller

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 12, 2024

Abstract Hepatic lipid accumulation, or Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD), is a significant risk factor for liver cancer. Despite the rising incidence of MASLD, underlying mechanisms steatosis and lipotoxicity remain poorly understood. Interestingly, accumulation also occurs during fasting, driven by mobilization adipose tissue-derived fatty acids into liver. However, how hepatocytes adapt to increased flux nutrient deprivation what differently in MASLD not known. To investigate differences handling response deficiency excess, we developed novel single-cell tissue imaging (scPhenomics) technique coupled with spatial proteomics. Our investigation revealed extensive remodeling droplet (LD) mitochondrial topology dietary conditions. Notably, fasted mice exhibited mitochondria-LD interactions, which were rarely observed Western Diet (WD)-fed mice. Spatial proteomics showed an increase PLIN5 expression, known mediator LD-mitochondria interaction, fasting. examine functional role interaction on handling, overexpressed variants. We found that phosphorylation state impacts its capacity form contact sites. S155A promoted organelle triglyceride (TG) synthesis, LD expansion fed control diet. Conversely, S155E expressing cells had fewer LDs sites contained less TG. Wild-type (WT) overexpression WD-fed reduced improved redox despite continued WD consumption. These findings highlight importance interactions metabolism, revealing critical mechanism maintain homeostasis metabolic stress. study underscores potential utility targeting therapeutic intervention.

Language: Английский

Versatile organic fluorescent probes for visualizing the dynamics of lipid droplets DOI

Mingyue Cao,

Yunting Liu,

Caihong Xiang

et al.

Coordination Chemistry Reviews, Journal Year: 2024, Volume and Issue: 522, P. 216181 - 216181

Published: Sept. 5, 2024

Language: Английский

Citations

18
A novel dual-channel fluorescent probe for the detection of peroxynitrite anions and lipid droplets in epileptic disease DOI

Yingxin Guo,

Huawei Huang, Qian Zhang

et al.

Analytica Chimica Acta, Journal Year: 2025, Volume and Issue: 1350, P. 343863 - 343863

Published: Feb. 24, 2025

Language: Английский

Citations

1
Moving the fat: Emerging roles of rab GTPases in the regulation of lipid droplet contact sites DOI Creative Commons

Mariano Alonso-Bivou,

Albert Pol, Harriet P. Lo

et al.

Current Opinion in Cell Biology, Journal Year: 2025, Volume and Issue: 93, P. 102466 - 102466

Published: Feb. 1, 2025

Lipid droplets (LDs) play crucial roles in lipid metabolism, energy homeostasis, and cellular stress. Throughout their lifecycle, LDs establish membrane contact sites (MCSs) with the endoplasmic reticulum, mitochondria, peroxisomes, endosomes, lysosomes, phagosomes. LD MCSs are dynamically generated response to metabolic or immune cues ensure that lipids (and proteins) timely delivered optimize valuable substrates avoid lipotoxicity. It is increasingly evident many Rab GTPases involved dynamics. Here, we summarize our current understanding of how when proteins drive generation regulate a variety functions.

Language: Английский

Citations

0
Bioactive lipid signaling and lipidomics in macrophage polarization: Impact on inflammation and immune regulation DOI Creative Commons
Juan Pablo Rodríguez, Javier Casas, Marı́a A. Balboa

et al.

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 16

Published: Feb. 14, 2025

Macrophages, crucial innate immune cells, defend against pathogens and resolve inflammation, maintaining tissue balance. They perform phagocytosis, present antigens to T bond adaptive immunity through various activation states. Classical is associated with Th1 responses interferon γ production, while alternative activation, induced by interleukin 4, characterized increased endocytosis, reduced secretion of pro-inflammatory cytokines, roles in immunoregulation remodeling. Although these represent opposite extremes observed vitro , the remarkable plasticity macrophages allows for a wide spectrum phenotypes that are complex characterize experimentally. While application omics techniques has resulted significant advances characterization macrophage polarization, lipidomic studies have received lesser attention. Beyond their role as structural components energy sources, lipids function signaling molecules regulate thereby shaping responses. This work reviews interaction between lipid exploring how metabolism influences phenotype function. These insights offer potential therapeutic strategies immune-mediated diseases inflammation-related disorders, including inflammaging.

Language: Английский

Citations

0
Expression of AMPK and PLIN2 in the regulation of lipid metabolism and oxidative stress in bitches with open cervix pyometra DOI Creative Commons
Xin Deng, Hongxing Liu, Wei Zhao

et al.

BMC Veterinary Research, Journal Year: 2025, Volume and Issue: 21(1)

Published: March 13, 2025

Abstract The pathogenesis of canine pyometra is multifactorial, involving hormonal imbalances, aberrant immune responses, and metabolic dysregulation includes lipid metabolism oxidative stress. This study focuses on stress, revealing the key regulatory role AMPK PLIN2 in pyometra. Bitches with open cervix (n:8) healthy bitches undergoing elective ovariohysterectomy (n:4) were enrolled to study. In experiment one, serum tissue levels Malondialdehyde (MDA) Superoxide Dismutase (SOD) activity assessed. Additionally, uterine histopathological analysis, expressions determined through immunohistochemistry. Furthermore, inflammation, metabolism-related factors evaluated using Western blot analysis. two, primary cell cultures prepared from endometrial cells dogs control group. Cultured epithelial treated lipopolysaccharide (LPS) along oleic acid (OA) induce an inflammatory response. Tissue MDA SOD greater Accumulated droplets observed phosphorylation expression significantly increased related synthesis proteins such as ACC1, FASN, SREBP-1c, was upregulated, while PPARα PGC1α downregulated activation not only restores PGC1α, but also effectively alleviates inflammation stress elucidated, thus contributing dogs.

Language: Английский

Citations

0
Mitochondria-organelle crosstalk in establishing compartmentalized metabolic homeostasis DOI
Brandon Chen, Costas A. Lyssiotis, Yatrik M. Shah

et al.

Molecular Cell, Journal Year: 2025, Volume and Issue: 85(8), P. 1487 - 1508

Published: April 1, 2025

Language: Английский

Citations

0
Imaging and proteomics toolkits for studying organelle contact sites DOI Creative Commons
Rico Gamuyao, Chi‐Lun Chang

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

Published: Sept. 24, 2024

Organelle contact sites are regions where two heterologous membranes juxtaposed by molecular tethering complexes. These important in inter-organelle communication and cellular functional integration. However, visualizing these minute foci identifying site proteomes have been challenging. In recent years, fluorescence-based methods developed to visualize the dynamic physical interaction of organelles while proximity labeling approaches facilitate profiling at sites. this review, we explain design principle for reporters: a dual-organelle mechanism based on how endogenous tethers and/or complexes localize We classify reporters into three categories: (i) single-protein systems, (ii) two-component systems with activated reporter signal upon organelle proximity, (iii) proteomes. also highlight advanced imaging analysis high temporal-spatial resolution use machine-learning algorithms detecting

Language: Английский

Citations

3
An organelle tango controls lipid metabolism DOI

Johannes Pilic,

Tatjana Kleele

Nature Cell Biology, Journal Year: 2024, Volume and Issue: 26(8), P. 1227 - 1228

Published: July 5, 2024

Language: Английский

Citations

0
Imaging interorganelle contacts at a glance DOI
Maria Clara Zanellati, Chih-Hsuan Hsu, Sarah Cohen

et al.

Journal of Cell Science, Journal Year: 2024, Volume and Issue: 137(20)

Published: Oct. 15, 2024

Eukaryotic cells are compartmentalized into membrane-bound organelles that must coordinate their responses to stimuli. One way communicate is via membrane contact sites (MCSs), of close apposition between used for the exchange ions, lipids and information. In this Cell Science at a Glance article accompanying poster, we describe an explosion new methods have led exciting progress in area discuss key examples how these advanced our understanding MCSs. We diffraction-limited super-resolution fluorescence imaging approaches provided important insight biology interorganelle communication. also development multiple proximity-based has enabled detection MCSs with high accuracy precision. Finally, assess recent advances electron microscopy (EM), considered gold standard detecting MCSs, allowed visualization associated proteins 3D ever greater resolution.

Language: Английский

Citations

0
Neurons and astrocytes have distinct organelle signatures and responses to stress DOI Open Access
Shannon N. Rhoads,

Wen-Wei Dong,

Chih-Hsuan Hsu

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 30, 2024

Summary Neurons and astrocytes play critical yet divergent roles in brain physiology neurological conditions. Intracellular organelles are integral to cellular function. However, an in-depth characterization of live cells has not been performed. Here, we used multispectral imaging simultaneously visualize six – endoplasmic reticulum (ER), lysosomes, mitochondria, peroxisomes, Golgi, lipid droplets primary rodent neurons astrocytes. We generated a dataset 173 Z-stack 99 time-lapse images accompanied by quantitative analysis 1418 metrics (the “organelle signature”). Comparative revealed clear cell-type specificity organelle morphology interactions. were characterized prominent mitochondrial composition interactions, while contained more lysosomes droplet Additionally, displayed robust response than acute oxidative or ER stress. Our data provide systems-level neuron astrocyte that can be reference for understanding cell- type-specific disease.

Language: Английский

Citations

0