N88S seipin-related seipinopathy is a lipidopathy associated with loss of iron homeostasis DOI Creative Commons

Mariana O. Ribeiro,

Mafalda Oliveira,

Verónica Nogueira

и другие.

Research Square (Research Square), Год журнала: 2024, Номер unknown

Опубликована: Окт. 11, 2024

Abstract Background Seipin is a protein encoded by the BSCL2 gene in humans and SEI1 yeast, forming an Endoplasmic Reticulum (ER)-bound homo-oligomer. This oligomer crucial targeting ER-lipid droplet (LD) contact sites, facilitating delivery of triacylglycerol (TG) to nascent LDs. Mutations BSCL2, particularly N88S S90L, lead seipinopathies, which correspond cohort motor neuron diseases (MNDs) characterized accumulation misfolded seipin into inclusion bodies (IBs) cellular dysfunctions. Methods Quantitative untargeted mass spectrometric proteomic lipidomic analyses were conducted examine changes lipid abundance wild-type (WT) versus seipin-expressing mutant cells. Differentially expressed proteins categorized functional networks highlight altered functions signaling pathways. Statistical comparisons made using unpaired, two-tailed Student's t-tests or two-way ANOVA. P-values < 0.05 are considered significant. Results In well-established yeast model seipinopathy, forms IBs exhibits higher levels ER stress, leading decreased cell viability due increased reactive oxygen species (ROS), oxidative damage, peroxidation, reduced antioxidant activity. Proteomic revealed alterations phosphatidic acid (PA) levels, associated with disrupted inositol metabolism flux towards phospholipid biosynthesis. Importantly, deregulation contributed stress beyond misfolding IB formation. Additionally, exhibited deregulated iron (Fe) homeostasis during lifespan. cells showed impaired ability cope deficiency. was linked expression Aft1p-controlled regulon genes, including mRNA-binding CTH2 high-affinity transport system member FET3, p38/Hog1p- Msn2p/Msn4p-dependent manner. we unraveled novel link between activation expressing mutation. Despite accumulation, this not stress. Conclusions The study highlights that effects mutation extend misfolding, significant disruptions homeostasis. research marks advance understanding defining roles pathways contribute human seipinopathy. Altered processes, as well potential therapeutic targets biomarkers, identified can be explored translational studies models.

Язык: Английский

N88S seipin-related seipinopathy is a lipidopathy associated with loss of iron homeostasis DOI Creative Commons

Mariana O. Ribeiro,

Mafalda Oliveira,

Verónica Nogueira

и другие.

Cell Communication and Signaling, Год журнала: 2025, Номер 23(1)

Опубликована: Янв. 7, 2025

Seipin is a protein encoded by the BSCL2 gene in humans and SEI1 yeast, forming an Endoplasmic Reticulum (ER)-bound homo-oligomer. This oligomer crucial targeting ER-lipid droplet (LD) contact sites, facilitating delivery of triacylglycerol (TG) to nascent LDs. Mutations BSCL2, particularly N88S S90L, lead seipinopathies, which correspond cohort motor neuron diseases (MNDs) characterized accumulation misfolded seipin into inclusion bodies (IBs) cellular dysfunctions. Quantitative untargeted mass spectrometric proteomic lipidomic analyses were conducted examine changes lipid abundance wild-type (WT) versus seipin-expressing mutant cells. Differentially expressed proteins categorized functional networks highlight altered functions signaling pathways. Statistical comparisons made using unpaired Student's t-tests or two-way ANOVA followed Tukey´s / Šídák's multiple tests. P-values < 0.05 are considered significant. In well-established yeast model seipinopathy, forms IBs exhibits higher levels ER stress, leading decreased cell viability due increased reactive oxygen species (ROS), oxidative damage, peroxidation, reduced antioxidant activity. Proteomic revealed alterations phosphatidic acid (PA) levels, associated with disrupted inositol metabolism flux towards phospholipid biosynthesis. Importantly, deregulation contributed stress beyond misfolding IB formation. Additionally, exhibited deregulated iron (Fe) homeostasis during lifespan. cells showed impaired ability cope deficiency. was linked expression Aft1p-controlled regulon genes, including mRNA-binding CTH2 high-affinity transport system member FET3, p38/Hog1p- Msn2p/Msn4p-dependent manner. we unraveled novel link between activation expressing mutation. Despite accumulation, this not stress. The study highlights that effects mutation extend misfolding, significant disruptions homeostasis. research marks substantial advance understanding defining roles pathways contribute human seipinopathy. Altered processes, as well potential therapeutic targets biomarkers, identified can be explored translational studies models.

Язык: Английский

Процитировано

0
The [2Fe‐2S] cluster of mitochondrial outer membrane protein mitoNEET has an O2‐regulated nitric oxide access tunnel DOI Creative Commons
T Hoang,

Meritxell Wu‐Lu,

Alberto Collauto

и другие.

FEBS Letters, Год журнала: 2025, Номер unknown

Опубликована: Янв. 5, 2025

The mitochondrial outer membrane iron-sulphur ([Fe-S]) protein mitoNEET has been extensively studied as a target of the anti-inflammatory and type-2 diabetes drug pioglitazone affecting respiratory rate. Despite these extensive past studies, its molecular function yet to be discovered. Here, we applied an interdisciplinary approach discovered explicit nitric oxide (NO) access site [2Fe-2S] cluster. We found that O

Язык: Английский

Процитировано

0
Iron sensing, signalling and acquisition by microbes and plants under environmental stress: Use of iron-solubilizing bacteria in crop biofortification for sustainable agriculture DOI
Suman Chaudhary, S. S. Sindhu

Plant Science, Год журнала: 2025, Номер unknown, С. 112496 - 112496

Опубликована: Апрель 1, 2025

Язык: Английский

Процитировано

0
N88S seipin-related seipinopathy is a lipidopathy associated with loss of iron homeostasis DOI Creative Commons

Mariana O. Ribeiro,

Mafalda Oliveira,

Verónica Nogueira

и другие.

Research Square (Research Square), Год журнала: 2024, Номер unknown

Опубликована: Окт. 11, 2024

Abstract Background Seipin is a protein encoded by the BSCL2 gene in humans and SEI1 yeast, forming an Endoplasmic Reticulum (ER)-bound homo-oligomer. This oligomer crucial targeting ER-lipid droplet (LD) contact sites, facilitating delivery of triacylglycerol (TG) to nascent LDs. Mutations BSCL2, particularly N88S S90L, lead seipinopathies, which correspond cohort motor neuron diseases (MNDs) characterized accumulation misfolded seipin into inclusion bodies (IBs) cellular dysfunctions. Methods Quantitative untargeted mass spectrometric proteomic lipidomic analyses were conducted examine changes lipid abundance wild-type (WT) versus seipin-expressing mutant cells. Differentially expressed proteins categorized functional networks highlight altered functions signaling pathways. Statistical comparisons made using unpaired, two-tailed Student's t-tests or two-way ANOVA. P-values < 0.05 are considered significant. Results In well-established yeast model seipinopathy, forms IBs exhibits higher levels ER stress, leading decreased cell viability due increased reactive oxygen species (ROS), oxidative damage, peroxidation, reduced antioxidant activity. Proteomic revealed alterations phosphatidic acid (PA) levels, associated with disrupted inositol metabolism flux towards phospholipid biosynthesis. Importantly, deregulation contributed stress beyond misfolding IB formation. Additionally, exhibited deregulated iron (Fe) homeostasis during lifespan. cells showed impaired ability cope deficiency. was linked expression Aft1p-controlled regulon genes, including mRNA-binding CTH2 high-affinity transport system member FET3, p38/Hog1p- Msn2p/Msn4p-dependent manner. we unraveled novel link between activation expressing mutation. Despite accumulation, this not stress. Conclusions The study highlights that effects mutation extend misfolding, significant disruptions homeostasis. research marks advance understanding defining roles pathways contribute human seipinopathy. Altered processes, as well potential therapeutic targets biomarkers, identified can be explored translational studies models.

Язык: Английский

Процитировано

0