DNA damage promotes ER stress resistance through elevation of unsaturated phosphatidylcholine in Caenorhabditis elegans

Deng, Jianhui; Bai, Xue; Tang, Haiqing; Pang, Shijin

doi:10.1074/jbc.ra120.016083

Cited by 20 publications

(17 citation statements)

References 63 publications

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“…stress, thus enhancing cellular maintenance (Deng et al, 2021). Intriguingly, the neurons and C. elegans somatic cells share some common features, as they are both postmitotic cells that cannot proliferate and are irreplaceable.…”

Section: Phosphatidylcholine and Brain Agingmentioning

confidence: 99%

“…The contents of unsaturated PC are increased in the somatic cells of C. elegans upon DNA damage, which represents an aging risk factor. Moreover, the elevation of unsaturated PCs is critical for promoting the ER UPR without causing ER stress, thus enhancing cellular maintenance ( Deng et al, 2021 ). Intriguingly, the neurons and C. elegans somatic cells share some common features, as they are both postmitotic cells that cannot proliferate and are irreplaceable.…”

Section: Phosphatidylcholinementioning

confidence: 99%

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The Crucial Roles of Phospholipids in Aging and Lifespan Regulation

2021

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Phospholipids are major membrane lipids that consist of lipid bilayers. This basic cellular structure acts as a barrier to protect the cell against various environmental insults and more importantly, enables multiple cellular processes to occur in subcellular compartments. Numerous studies have linked the complexity of membrane lipids to signal transductions, organelle functions, as well as physiological processes, and human diseases. Recently, crucial roles for membrane lipids in the aging process are beginning to emerge. In this study, we summarized current advances in our understanding of the relationship between membrane lipids and aging with an emphasis on phospholipid species. We surveyed how major phospholipid species change with age in different organisms and tissues, and some common patterns of membrane lipid change during aging were proposed. Further, the functions of different phospholipid molecules in regulating healthspan and lifespan, as well as their potential mechanisms of action, were also discussed.

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Section: Phosphatidylcholine and Brain Agingmentioning

confidence: 99%

Section: Phosphatidylcholinementioning

confidence: 99%

The Crucial Roles of Phospholipids in Aging and Lifespan Regulation

2021

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“…In our transcriptomic data, we find that KD of cdk-12 up-regulates innate immune response genes independent of DAF-16 activation (Figure S3F, G). Further, cdk-12 depletion conferred increased heat stress resistance (Figure S3H, I) and hsp-4::gfp (Endoplasmic Reticulum Chaperon BiP ortholog) expression (Figure S3J), as has been reported for DNA damage (30,31). Thus, RNAi Further, we wanted to visualize the role of CDK-12 in somatic DNA damage.…”

Section: Cdk-12 Is Required For Efficient Dna Damage Repairmentioning

confidence: 69%

A cell non-autonomous FOXO/DAF-16-mediated germline quality assurance program that responds to somatic DNA damage

Sarkar

Rautela

Goyala

et al. 2022

Preprint

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Germline integrity is critical for progeny fitness. Organisms deploy the DNA damage response (DDR) signalling to protect germline from genotoxic stress, facilitating cell-cycle arrest of germ cells and DNA repair or their apoptosis. Cell-autonomous regulation of germline quality is well-studied; however, how quality is enforced cell non-autonomously on sensing somatic DNA damage is less known. Using Caenorhabditis elegans, we show that DDR disruption, only in the uterus, when insulin-IGF-1 signalling (IIS) is low, arrests germline development and induces sterility in a FOXO/DAF-16 transcription factor (TF)-dependent manner. Without FOXO/DAF-16, germ cells of the IIS mutant escape arrest to produce poor quality oocytes, showing that the TF imposes strict quality control during low IIS. In response to low IIS in neurons, FOXO/DAF-16 works cell autonomously as well as non-autonomously to facilitate the arrest. Activated FOXO/DAF-16 promotes transcription of checkpoint and DDR genes, protecting germline integrity. However, on reducing DDR during low IIS, the TF decreases ERK/MPK-1 signaling below a threshold, and transcriptionally downregulates genes involved in spermatogenesis-to-oogenesis switch as well as cdk-1/Cyclin B to promote germline arrest. Altogether, our study reveals how cell non-autonomous function of FOXO/DAF-16 promotes germline quality and progeny fitness in response to somatic DNA damage.Significance StatementReproductive decisions are supervised processes that take into account various inputs like cellular energy availability and status of damage repair in order to ensure healthy progeny. In this study, we show that the absence of optimal DNA damage repair in the somatic uterine tissues prevents oocyte development by the cell-autonomous as well non-autonomous function of activated FOXO transcription factor DAF-16. Thus, this study elucidates a new surveillance role of FOXO/DAF-16 in somatic tissues that ensures progeny fitness.

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“…Thin-layer chromatography (TLC) was performed as previously described [ 59 , 60 ] with modifications. 50,000 L4 worms were collected and washed with M9 to remove bacteria, and were sonicated in 0.25 mL PBS.…”

Section: Methodsmentioning

confidence: 99%

Phosphatidylcholine mediates the crosstalk between LET-607 and DAF-16 stress response pathways

Pang

et al. 2021

PLoS Genet

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Coordinated regulation of stress response pathways is crucial for cellular homeostasis. However, crosstalk between the different stress pathways and the physiological significance of this crosstalk remain poorly understood. In this study, using the model organism C. elegans, we discovered that suppression of the transcription factor LET-607/CREBH, a regulator of cellular defense and proteostatic responses, triggers adaptive induction of DAF-16-dependent stress responses. Suppression of LET-607 improves stress resistance and extends C. elegans lifespan in a DAF-16-dependent manner. We identified the sphingomyelin synthase SMS-5 to be a central mediator in the communication between LET-607 and DAF-16. SMS-5 reduces the contents of unsaturated phosphatidylcholine (PC), which activates DAF-16 through ITR-1-dependent calcium signaling and calcium-sensitive kinase PKC-2. Our data reveal the significance of crosstalk between different stress pathways in animal fitness and identify LET-607/CREBH and specific PC as regulators of DAF-16 and longevity.

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DNA damage promotes ER stress resistance through elevation of unsaturated phosphatidylcholine in Caenorhabditis elegans

Cited by 20 publications

References 63 publications

The Crucial Roles of Phospholipids in Aging and Lifespan Regulation

The Crucial Roles of Phospholipids in Aging and Lifespan Regulation

A cell non-autonomous FOXO/DAF-16-mediated germline quality assurance program that responds to somatic DNA damage

Phosphatidylcholine mediates the crosstalk between LET-607 and DAF-16 stress response pathways

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