Optogenetic Strategies for Optimizing the Performance of Phospholipids Biosensors DOI Creative Commons
Yuanfa Yao,

Xiayan Lou,

Luhong Jin

et al.

Advanced Science, Journal Year: 2024, Volume and Issue: unknown

Published: July 29, 2024

High-performance biosensors play a crucial role in elucidating the intricate spatiotemporal regulatory roles and dynamics of membrane phospholipids. However, enhancing sensitivity imaging performance remains significant challenge. Here, optogenetic-based strategies are presented to optimize phospholipid biosensors. These involves presequestering unbound cell nucleus regulating their cytosolic levels with blue light minimize background signal interference detection, particularly under conditions high expression biosensor. Furthermore, optically controlled phase separation SunTag system employed generate punctate probes for substrate thereby amplifying biosensor signals visualization detection process. improved hold great potential understanding lipids live cells methodological insights this study might be valuable developing other high-performance

Language: Английский

The interconnective role of the UPS and autophagy in the quality control of cancer mitochondria DOI Creative Commons

Wanting Xu,

Lei Dong, Jiyan Dai

et al.

Cellular and Molecular Life Sciences, Journal Year: 2025, Volume and Issue: 82(1)

Published: Jan. 12, 2025

Uncontrollable cancer cell growth is characterized by the maintenance of cellular homeostasis through continuous accumulation misfolded proteins and damaged organelles. This review delineates roles two complementary synergistic degradation systems, ubiquitin–proteasome system (UPS) autophagy-lysosome system, in organelles for intracellular recycling. We emphasize interconnected decision-making processes systems maintaining homeostasis, such as biophysical state substrates, receptor oligomerization potentials (e.g., p62), compartmentalization capacities membrane structures). Mitochondria, hubs respiration metabolism, are implicated tumorigenesis. In subsequent sections, we thoroughly examine mechanisms mitochondrial quality control (MQC) preserving human cells. Notably, explored relationships between dynamics (fusion fission) various MQC processes—including UPS, proteases, mitophagy—in context repair pathways. Finally, assessed potential targeting (including molecular chaperones, dynamics, mitophagy biogenesis) therapeutic strategies. Understanding underlying may offer novel insights future therapies. highlights UPS degrading proteins, emphasizing substrate states, oligomerization, homeostasis. Innovatively links coordination to examining interplay these pathways varying degrees damage.

Language: Английский

Citations

2
PERK signaling promotes mitochondrial elongation by remodeling membrane phosphatidic acid DOI Creative Commons

Valerie Perea,

Christian M. Cole,

Justine Lebeau

et al.

The EMBO Journal, Journal Year: 2023, Volume and Issue: 42(15)

Published: June 12, 2023

Abstract Endoplasmic reticulum (ER) stress and mitochondrial dysfunction are linked in the onset pathogenesis of numerous diseases. This has led to considerable interest defining mechanisms responsible for regulating mitochondria during ER stress. The PERK signaling arm unfolded protein response (UPR) emerged as a prominent stress‐responsive pathway that regulates diverse aspects biology. Here, we show activity promotes adaptive remodeling membrane phosphatidic acid (PA) induce protective elongation acute We find is required stress‐dependent increases both cellular PA YME1L‐dependent degradation intramitochondrial transporter PRELID1. These two processes lead accumulation on outer where it can by inhibiting fission. Our results establish new role phospholipids demonstrate PERK‐dependent regulation adapts organellar shape

Language: Английский

Citations

37
The endoplasmic reticulum: Homeostasis and crosstalk in retinal health and disease DOI Creative Commons
Sarah X. Zhang, Josh J. Wang, Christopher R. Starr

et al.

Progress in Retinal and Eye Research, Journal Year: 2023, Volume and Issue: 98, P. 101231 - 101231

Published: Dec. 12, 2023

Language: Английский

Citations

23
The integrated stress response in metabolic adaptation DOI Creative Commons
Hyung Don Ryoo

Journal of Biological Chemistry, Journal Year: 2024, Volume and Issue: 300(4), P. 107151 - 107151

Published: March 9, 2024

The Integrated Stress Response (ISR) refers to signaling pathways initiated by stress-activated eIF2‹ kinases. Distinct kinases respond different stress signals, including amino acid deprivation and mitochondrial stress. Such stress-induced phosphorylation attenuates general mRNA translation and, at the same time, stimulates preferential of specific downstream factors orchestrate an adaptive gene expression program. In recent years, there have been significant new advances in our understanding ISR during metabolic adaptation. Here, I discuss those advances, reviewing among others activation mechanisms response addition, review how regulates changes impact physiology pathology various disease models.

Language: Английский

Citations

13
Homeostasis control in health and disease by the unfolded protein response DOI
Diego Acosta‐Alvear, Jonathan M. Harnoss, Peter Walter

et al.

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

Published: Nov. 5, 2024

Language: Английский

Citations

12
eIF2α Phosphorylation-ATF4 Axis-Mediated Transcriptional Reprogramming Mitigates Mitochondrial Impairment During ER Stress DOI Open Access
Lê Thị Thu Hiền, Jiyoung Yu, Hee‐Sung Ahn

et al.

Molecules and Cells, Journal Year: 2025, Volume and Issue: unknown, P. 100176 - 100176

Published: Jan. 1, 2025

Eukaryotic translation initiation factor 2α (eIF2α) phosphorylation, which regulates all three unfolded protein response pathways, helps maintain cellular homeostasis and overcome endoplasmic reticulum (ER) stress through transcriptional translational reprogramming. However, regulation of mitochondrial by eIF2α phosphorylation during ER is not fully understood. Here, we report that the phosphorylation-activating transcription 4 (ATF4) axis required for expression multiple factors (TFs) including nuclear erythroid 2-related 2 (Nrf2) their target genes responsible stress. phosphorylation-deficient (A/A) cells displayed dysregulated dynamics DNA replication, decreased oxidative complex proteins, impaired functions ATF4 overexpression suppressed impairment in A/A promoting downstream TFs genes. Our findings underscore importance phosphorylation-ATF4 maintaining reprogramming

Language: Английский

Citations

1
Endoplasmic Reticulum-Mitochondria Crosstalk in Fuchs Endothelial Corneal Dystrophy: Current Status and Future Prospects DOI Open Access
Anisha Kasi,

William Steidl,

Varun Kumar

et al.

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(3), P. 894 - 894

Published: Jan. 22, 2025

Fuchs endothelial corneal dystrophy (FECD) is a progressive and debilitating disorder of the endothelium (CE) that affects approximately 4% individuals over age 40. Despite burden disease, pathogenesis FECD remains poorly understood, treatment options are limited, highlighting need for deeper investigation into its underlying molecular mechanisms. Over past decade, studies have indicated independent contributions endoplasmic reticulum (ER) mitochondrial stress to FECD. However, there limited suggesting ER-mitochondria crosstalk in Recently, our lab established role chronic ER inducing dysfunction cells (CEnCs), indicating existence This paper aims provide comprehensive overview current understanding how contribute pathogenesis. The also reviews literature on mechanisms other diseases relevant

Language: Английский

Citations

1
Mapping stress-responsive signaling pathways induced by mitochondrial proteostasis perturbations DOI
Nicole Madrazo, Zinia Khattar, Evan T. Powers

et al.

Molecular Biology of the Cell, Journal Year: 2024, Volume and Issue: 35(5)

Published: March 27, 2024

Imbalances in mitochondrial proteostasis are associated with pathologic dysfunction implicated etiologically diverse diseases. This has led to considerable interest defining the mechanisms responsible for regulating mitochondria response stress. Numerous stress-responsive signaling pathways have been suggested regulate proteotoxic These include integrated stress (ISR), heat shock (HSR), and oxidative (OSR). Here, we define activated chronic perturbations by monitoring expression of sets genes regulated downstream each these published Perturb-seq datasets from K562 cells CRISPRi-depleted factors. Interestingly, find that ISR is preferentially chronic, genetically-induced stress, no other pathway showing significant activation. Further, demonstrate CRISPRi depletion mitochondria-localized proteins similarly shows preferential activation relative pathways. results both establish our gene set profiling approach as a viable strategy probe responsive induced specific organelles identify predominant disruption proteostasis.

Language: Английский

Citations

6
Pharmacologic activation of a compensatory integrated stress response kinase promotes mitochondrial remodeling in PERK-deficient cells DOI Creative Commons

Valerie Perea,

Kelsey R. Baron, Vivian Dolina

et al.

Cell chemical biology, Journal Year: 2023, Volume and Issue: 30(12), P. 1571 - 1584.e5

Published: Nov. 2, 2023

Language: Английский

Citations

15
UBXN1 maintains ER proteostasis and represses UPR activation by modulating translation DOI Creative Commons
Brittany A. Ahlstedt, Rakesh Ganji, Sirisha Mukkavalli

et al.

EMBO Reports, Journal Year: 2024, Volume and Issue: 25(2), P. 672 - 703

Published: Jan. 2, 2024

Abstract ER protein homeostasis (proteostasis) is essential for proper folding and maturation of proteins in the secretory pathway. Loss proteostasis can lead to accumulation misfolded or aberrant triggers unfolded response (UPR). In this study, we find that p97 adaptor UBXN1 an important negative regulator UPR. sensitizes cells stress activates This leads widespread upregulation transcriptional program. Using comparative, quantitative proteomics show deletion results a significant enrichment involved ER-quality control processes including those import. Notably, loss does not perturb p97-dependent ER-associated degradation (ERAD). Our studies indicate increases translation both resting ER-stressed cells. Surprisingly, process independent function. Taken together, our have identified new role repressing maintaining manner.

Language: Английский

Citations

4