ER-associated degradation ligase HRD1 links ER stress to DNA damage repair by modulating the activity of DNA-PKcs DOI

Zhiyuan Xiang,

Guixue Hou, Shanliang Zheng

et al.

Proceedings of the National Academy of Sciences, Journal Year: 2024, Volume and Issue: 121(37)

Published: Sept. 3, 2024

Proteostasis and genomic integrity are respectively regulated by the endoplasmic reticulum-associated protein degradation (ERAD) DNA damage repair signaling pathways, with both pathways essential for carcinogenesis drug resistance. How these coordinate each other remains unexplored. We found that ER stress specifically induces DNA-PKcs-regulated nonhomologous end joining (NHEJ) pathway to amend impede cell death. Intriguingly, sustained rapidly decreased activity of DNA-PKcs accumulated, facilitating a switch from adaptation This inactivation was caused increased KU70/KU80 degradation. Unexpectedly, ERAD ligase HRD1 efficiently destabilize classic nuclear HDAC1 in cytoplasm, catalyzing HDAC1's polyubiquitination at lysine 74, late stage stress. By abolishing HDAC1-mediated deacetylation, transmits signals nucleus. The resulting enhanced acetylation provides binding sites E3 TRIM25, promotion proteins. Both vitro vivo cancer models showed genetic or pharmacological inhibition HADC1 sensitizes colon cells inducers, including Food Drug Administration-approved celecoxib. antitumor effects combined approach were also observed patient-derived xenograft models. These findings identify mechanistic link between cytoplasm nucleus, indicating anticancer strategies may be developed induce severe while simultaneously inhibiting KU70/KU80/DNA-PKcs-mediated NHEJ signaling.

Language: Английский

ER remodeling via lipid metabolism DOI Creative Commons
Wonyul Jang, Volker Haucke

Trends in Cell Biology, Journal Year: 2024, Volume and Issue: 34(11), P. 942 - 954

Published: Feb. 23, 2024

Unlike most other organelles found in multiple copies, the endoplasmic reticulum (ER) is a unique singular organelle within eukaryotic cells. Despite its continuous membrane structure, encompassing more than half of cellular endomembrane system, ER subdivided into specialized sub-compartments, including morphological, contact site (MCS), and de novo biogenesis domains. In this review, we discuss recent emerging evidence indicating that, response to nutrient stress, cells undergo reorganization these sub-compartmental domains through two main mechanisms: non-destructive remodeling morphological via regulation MCS hitchhiking, destructive by ER-phagy. We further highlight propose critical role lipid metabolism during starvation.

Language: Английский

Citations

8
Assembly and fission of tubular carriers mediating protein sorting in endosomes DOI
Navin Gopaldass, Kai‐En Chen, Brett M. Collins

et al.

Nature Reviews Molecular Cell Biology, Journal Year: 2024, Volume and Issue: unknown

Published: June 17, 2024

Language: Английский

Citations

8
Unravelling the Mystery inside Cells by Using Single-Molecule Fluorescence Imaging DOI Creative Commons
Julian Zalejski, Jiachen Sun, Ashutosh Sharma

et al.

Journal of Imaging, Journal Year: 2023, Volume and Issue: 9(9), P. 192 - 192

Published: Sept. 19, 2023

Live-cell imaging is a powerful technique to study the dynamics and mechanics of various biological molecules like proteins, organelles, DNA, RNA. With rapid evolution optical microscopy, our understanding how these are implicated in cells’ most critical physiological roles deepens. In this review, we focus on spatiotemporal nanoscale live-cell at single molecule level allows for profound contributions towards new discoveries life science. This review will start by summarizing single-molecule tracking has been used analyze membrane dynamics, receptor–ligand interactions, protein–protein inner- extra-cellular transport, gene expression/transcription, whole organelle tracking. We then move current authors trying improve overcome limitations offering ways labeling proteins interest, multi-channel/color detection, improvements time-lapse imaging, methods programs colocalization movement targets. later discuss can be beneficial tool medical diagnosis. Finally, wrap up with future perspectives total internal reflection microscopy.

Language: Английский

Citations

16
ASTER-B regulates mitochondrial carotenoid transport and homeostasis DOI Creative Commons
Sepalika Bandara, Jean Moon, Srinivasagan Ramkumar

et al.

Journal of Lipid Research, Journal Year: 2023, Volume and Issue: 64(5), P. 100369 - 100369

Published: April 6, 2023

The scavenger receptor class B type 1 (SR-B1) facilitates uptake of cholesterol and carotenoids into the plasma membrane (PM) mammalian cells. Downstream SR-B1, ASTER-B protein mediates nonvesicular transport to mitochondria for steroidogenesis. Mitochondria also are place processing diapocarotenoids by β-carotene oxygenase-2. However, role these lipid proteins in carotenoid metabolism has not yet been established. Herein, we showed that recombinant StART-like lipid-binding domain ASTER-A preferentially binds oxygenated such as zeaxanthin. We established a novel assay demonstrated expressing A549 cells zeaxanthin mitochondria. In contrast, pure hydrocarbon is transported organelles, consistent with its metabolic vitamin A cytosol oxygenase-1. Depletion PM from methyl-β-cyclodextrin treatment enhanced but Loss-of-function assays siRNA absence accumulation ARPE19 confirmed pivotal this process. Together, our study human cell lines key player elucidated molecular basis compartmentalization nonprovitamin provitamin

Language: Английский

Citations

14
Loss of AMPK activity induces organelle dysfunction and oxidative stress during oocyte aging DOI Creative Commons

Linlin Hu,

Mei‐Hua Liao,

Yaxi Liu

et al.

Biology Direct, Journal Year: 2024, Volume and Issue: 19(1)

Published: April 23, 2024

Abstract Background Oocyte quality is critical for the mammalian reproduction due to its necessity on fertilization and early development. During aging, declined oocytes showing with organelle dysfunction oxidative stress lead infertility. AMP-activated protein kinase (AMPK) a serine/threonine which important energy homeostasis metabolism. Little known about potential relationship between AMPK oocyte aging. Results In present study we reported that was related low of under post ovulatory aging mechanism. We showed altered level during inhibition activity induced mouse maturation defect. Further analysis indicated similar upstream regulator PKD1, could reduce ROS avoid in oocytes, this might be regulation mitochondria function, since loss abnormal distribution, reduced ATP production mtDNA copy number mitochondria. Besides, also found ER Golgi apparatus distribution aberrant after inhibition, enhanced lysosome function observed. Conclusions Taken together, these data meiotic maturation.

Language: Английский

Citations

5
Role of endoplasmic reticulum stress-related unfolded protein response and its implications in dengue virus infection for biomarker development DOI
Biswadeep Das, Sagnika Samal, Hamida Hamdi

et al.

Life Sciences, Journal Year: 2023, Volume and Issue: 329, P. 121982 - 121982

Published: July 28, 2023

Language: Английский

Citations

13
Arf1-PI4KIIIβ positive vesicles regulate PI(3)P signaling to facilitate lysosomal tubule fission DOI Creative Commons
Maxime Boutry, Laura F. DiGiovanni, Nicholas D. Demers

et al.

The Journal of Cell Biology, Journal Year: 2023, Volume and Issue: 222(9)

Published: June 8, 2023

Formation and fission of tubules from autolysosomes, endolysosomes, or phagolysosomes are required for lysosome reformation. However, the mechanisms governing these processes in different lysosomal organelles poorly understood. Thus, role phosphatidylinositol-4-phosphate (PI(4)P) is unclear as it was shown to promote formation but proposed inhibit tubule on autolysosomes because loss PI4KIIIβ causes extensive tubulation. Using super-resolution live-cell imaging, we show that Arf1-PI4KIIIβ positive vesicles recruited sites phagolysosomes. Moreover, PI(4)P form autolysosomal increased tubulation caused by represents impaired fission. At site fission, propose mediate a PI(3)P signal lysosomes process requiring lipid transfer protein SEC14L2. Our findings indicate their regulation critical components machinery.

Language: Английский

Citations

11
Endoplasmic Reticulum Membrane Homeostasis and the Unfolded Protein Response DOI
Robert Ernst, Mike F. Renne, Aamna Jain

et al.

Cold Spring Harbor Perspectives in Biology, Journal Year: 2024, Volume and Issue: 16(8), P. a041400 - a041400

Published: Jan. 22, 2024

Robert Ernst1,2, Mike F. Renne1,2, Aamna Jain1,2 and Alexander von der Malsburg1,2 1Medical Biochemistry Molecular Biology, Medical Faculty, Saarland University, 66421 Homburg, Germany 2Preclinical Center for Signaling (PZMS), Correspondence: robert.ernst{at}uks.eu

Language: Английский

Citations

4
The Role of Endoplasmic Reticulum Stress in Metabolic Diseases DOI
Fı̇rdevs Sak, Fatma Şengül, Hüsamettin Vatansev

et al.

Metabolic Syndrome and Related Disorders, Journal Year: 2024, Volume and Issue: 22(7), P. 487 - 493

Published: April 26, 2024

The endoplasmic reticulum (ER), the center of protein folding, also controls cell's life-and-death signaling mechanisms. ER stress caused by unfolded or misfolded proteins leads to activation response (UPR) in cell. UPR utilizes three main pathways restore disrupted homeostasis. These are kinase R-like kinase, inositol-requiring enzyme 1, and activating transcription factor 6. Studies have reported that (ERS) plays a role pathogenesis metabolic disorders such as diabetes, obesity, atherosclerosis, nonalcoholic liver disease. This review will briefly discuss ERS these diseases.

Language: Английский

Citations

4
Tubular ER structures shaped by ER-phagy receptors engage in stress-induced Golgi bypass DOI
Min Seok Song, Hun Ju Sim,

Sung Ho Eun

et al.

Developmental Cell, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 1, 2025

Language: Английский

Citations

0