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Lysophosphatidylcholine acyltransferase 1 controls the mitochondrial reactive oxygen species generation and survival of the retinal photoreceptor cells [P8 photoreceptor]

ABSTRACT: Lysophosphatidylcholine acyltransferase 1 controls the mitochondrial reactive oxygen species generation and survival of the retinal photoreceptor cells [P8 photoreceptor]

PROVIDER: PRJNA766601 | ENA |

REPOSITORIES: ENA

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Lysophosphatidylcholine acyltransferase 1 controls the mitochondrial reactive oxygen species generation and survival of the retinal photoreceptor cells [P8 photoreceptor]

Project description:Due to the high energy demands and characteristic morphology, retinal photoreceptor cells require a specialized lipid metabolism for survival and function. This study focused on the roles of saturated fatty acids and their metabolism. A frameshift mutation of lysophosphatidylcholine acyltransferase 1 (Lpcat1), introducing saturated fatty acids into lysophosphatidylcholine to produce disaturated phosphatidylcholine (PC), has been reported to cause spontaneous retinal degeneration in mice (rd11 mice).　In this study, we performed a detailed characterization of Lpcat1 in the retina and found that Lpcat1 deficiency induces light-independent and photoreceptor-specific apoptosis in mice. Lipidomic analyses of the retina and isolated photoreceptor outer segment (OS) suggested that loss of Lpcat1 affects disaturated PC production and the proper cellular fatty acid flux, presumably by altering saturated fatty acyl-CoA availabilities. Furthermore, we demonstrated that Lpcat1 deletion increased mitochondrial reactive oxygen species (ROS) levels in photoreceptor cells, but not in other retinal cells without affecting the OS structure and trafficking of OS-localized proteins. These results suggest that the LPCAT1-dependent production of disaturated PC is critical for metabolic adaptation during photoreceptor maturation. Our findings highlight the therapeutic potential of saturated fatty acid metabolism in photoreceptor cell degeneration-related retinal diseases.

2022-01-01 | GSE184817 | GEO

Lysophosphatidylcholine acyltransferase 1 controls the mitochondrial reactive oxygen species generation and survival of the retinal photoreceptor cells [2w Retina]

Project description:Due to the high energy demands and characteristic morphology, retinal photoreceptor cells require the specialized lipid metabolism for survival and functions. In this study, we focus on the roles of saturated fatty acids and their metabolism in these processes. Frame-shift mutation of lysophosphatidylcholine acyltransferase 1 (Lpcat1), which introduces saturated fatty acid into lysophosphatidylcholine to produce disaturated phosphatidylcholine (PC), has been reported as a causative for spontaneous retinal degeneration in mice (rd11 mice). However, the molecular basis of retinal degeneration caused by Lpcat1 mutation remains unclear. Here, we report that Lpcat1 deficiency induces light-independent and photoreceptor-specific apoptosis in mice. Lipidomic analyses of retina and isolated photoreceptor outer segment (OS) suggested that loss of Lpcat1 affects not only disaturated PC production, but also the proper cellular fatty acid flux presumably through altering saturated fatty acyl-CoA availabilities. Furthermore, we demonstrated that Lpcat1 deletion increased mitochondrial reactive oxygen species (ROS) levels in photoreceptor cells, but not in other retinal cells, without affecting the OS structure and trafficking of OS localized proteins. These results suggested that LPCAT1-dependent production of disaturated PC is critical for metabolic adaptation during photoreceptor maturation. Our findings highlight the therapeutic potential of saturated fatty acid metabolism in photoreceptor cell degeneration-related retinal diseases.

2022-01-01 | GSE184815 | GEO

Lysophosphatidylcholine acyltransferase 1 controls the mitochondrial reactive oxygen species generation and survival of the retinal photoreceptor cells

Project description:Lysophosphatidylcholine acyltransferase 1 controls the mitochondrial reactive oxygen species generation and survival of the retinal photoreceptor cells

| PRJNA766595 | ENA

Lysophosphatidylcholine acyltransferase 1 controls the mitochondrial reactive oxygen species generation and survival of the retinal photoreceptor cells [2w Retina]

Project description:Lysophosphatidylcholine acyltransferase 1 controls the mitochondrial reactive oxygen species generation and survival of the retinal photoreceptor cells [2w Retina]

| PRJNA766600 | ENA

Lysophosphatidylcholine acyltransferase 1 controls mitochondrial reactive oxygen species generation and survival of retinal photoreceptor cells.

Project description:Due to their high energy demands and characteristic morphology, retinal photoreceptor cells require a specialized lipid metabolism for survival and function. Accordingly, dysregulation of lipid metabolism leads to the photoreceptor cell death and retinal degeneration. Mice bearing a frameshift mutation in the gene encoding lysophosphatidylcholine acyltransferase 1 (Lpcat1), which produces saturated phosphatidylcholine (PC) composed of two saturated fatty acids, has been reported to cause spontaneous retinal degeneration in mice; however, the mechanism by which this mutation affects degeneration is unclear. In this study, we performed a detailed characterization of LPCAT1 in the retina and found that genetic deletion of Lpcat1 induces light-independent and photoreceptor-specific apoptosis in mice. Lipidomic analyses of the retina and isolated photoreceptor outer segment (OS) suggested that loss of Lpcat1 not only decreased saturated PC production but also affected membrane lipid composition, presumably by altering saturated fatty acyl-CoA availability. Furthermore, we demonstrated that Lpcat1 deletion led to increased mitochondrial reactive oxygen species levels in photoreceptor cells, but not in other retinal cells, and did not affect the OS structure or trafficking of OS-localized proteins. These results suggest that the LPCAT1-dependent production of saturated PC plays critical roles in photoreceptor maturation. Our findings highlight the therapeutic potential of saturated fatty acid metabolism in photoreceptor cell degeneration-related retinal diseases.

| S-EPMC9136105 | biostudies-literature

Lysophosphatidylcholine acyltransferase 1 controls the mitochondrial reactive oxygen species generation and survival of the retinal photoreceptor cells

Project description:This SuperSeries is composed of the SubSeries listed below.

2022-01-01 | GSE184818 | GEO

Loss of lysophosphatidylcholine acyltransferase 1 leads to photoreceptor degeneration in rd11 mice.

Project description:Retinal degenerative diseases, such as retinitis pigmentosa and Leber congenital amaurosis, are a leading cause of untreatable blindness with substantive impact on the quality of life of affected individuals and their families. Mouse mutants with retinal dystrophies have provided a valuable resource to discover human disease genes and helped uncover pathways critical for photoreceptor function. Here we show that the rd11 mouse mutant and its allelic strain, B6-JR2845, exhibit rapid photoreceptor dysfunction, followed by degeneration of both rods and cones. Using linkage analysis, we mapped the rd11 locus to mouse chromosome 13. We then identified a one-nucleotide insertion (c.420-421insG) in exon 3 of the Lpcat1 gene. Subsequent screening of this gene in the B6-JR2845 strain revealed a seven-nucleotide deletion (c.14-20delGCCGCGG) in exon 1. Both sequence changes are predicted to result in a frame-shift, leading to premature truncation of the lysophosphatidylcholine acyltransferase-1 (LPCAT1) protein. LPCAT1 (also called AYTL2) is a phospholipid biosynthesis/remodeling enzyme that facilitates the conversion of palmitoyl-lysophosphatidylcholine to dipalmitoylphosphatidylcholine (DPPC). The analysis of retinal lipids from rd11 and B6-JR2845 mice showed substantially reduced DPPC levels compared with C57BL/6J control mice, suggesting a causal link to photoreceptor dysfunction. A follow-up screening of LPCAT1 in retinitis pigmentosa and Leber congenital amaurosis patients did not reveal any obvious disease-causing mutations. Previously, LPCAT1 has been suggested to be critical for the production of lung surfactant phospholipids and biosynthesis of platelet-activating factor in noninflammatory remodeling pathway. Our studies add another dimension to an essential role for LPCAT1 in retinal photoreceptor homeostasis.

| S-EPMC2932565 | biostudies-literature

Paenibacillus sp. P8 strain:P8

Project description:Paenibacillus sp. P8 strain:P8 Genome sequencing

| PRJNA1183732 | ENA

Clostridioides difficile P8 strain:P8

Project description:Clostridioides difficile P8 strain:P8 Genome sequencing and assembly

| PRJNA85973 | ENA

Sphingopyxis sp. P8 strain:P8

Project description:Sphingopyxis sp. P8 strain:P8 Genome sequencing and assembly

| PRJNA657447 | ENA