A dynamic role for transcription factors in restoring transcription through mitosis
Biochem Soc Trans. 2024 Mar 25:BST20231022. doi: 10.1042/BST20231022. Online ahead of print.ABSTRACTMitosis involves intricate steps, such as DNA condensation, nuclear membrane disassembly, and phosphorylation cascades that temporarily halt gene transcription. Despite this disruption, daughter cells remarkably retain the parent cell's gene expression pattern, allowing for efficient transcriptional memory after division. Early studies in mammalian cells suggested that transcription factors (TFs) mark genes for swift reactivation, a phenomenon termed 'mitotic bookmarking', but conflicting data emerged regarding TF presence o...
Source: Biochemical Society Transactions - March 25, 2024 Category: Biochemistry Authors: Marek A Budzy ński Alexander K L Wong Armin Faghihi Sheila S Teves Source Type: research

Insights into the dynamics of the Ca2+ release-activated Ca2+ channel pore-forming complex Orai1
Biochem Soc Trans. 2024 Mar 25:BST20230815. doi: 10.1042/BST20230815. Online ahead of print.ABSTRACTAn important calcium (Ca2+) entry pathway into the cell is the Ca2+ release-activated Ca2+ (CRAC) channel, which controls a series of downstream signaling events such as gene transcription, secretion and proliferation. It is composed of a Ca2+ sensor in the endoplasmic reticulum (ER), the stromal interaction molecule (STIM), and the Ca2+ ion channel Orai in the plasma membrane (PM). Their activation is initiated by receptor-ligand binding at the PM, which triggers a signaling cascade within the cell that ultimately causes st...
Source: Biochemical Society Transactions - March 25, 2024 Category: Biochemistry Authors: Maximilian Fr öhlich Julia S öllner Isabella Derler Source Type: research

Complex I activity in hypoxia: implications for oncometabolism
Biochem Soc Trans. 2024 Mar 25:BST20230189. doi: 10.1042/BST20230189. Online ahead of print.ABSTRACTCertain cancer cells within solid tumors experience hypoxia, rendering them incapable of oxidative phosphorylation (OXPHOS). Despite this oxygen deficiency, these cells exhibit biochemical pathway activity that relies on NAD+. This mini-review scrutinizes the persistent, residual Complex I activity that oxidizes NADH in the absence of oxygen as the electron acceptor. The resulting NAD+ assumes a pivotal role in fueling the α-ketoglutarate dehydrogenase complex, a critical component in the oxidative decarboxylation branch of...
Source: Biochemical Society Transactions - March 25, 2024 Category: Biochemistry Authors: Christos Chinopoulos Source Type: research

CRISPRi: a way to integrate iPSC-derived neuronal models
Biochem Soc Trans. 2024 Mar 25:BST20230190. doi: 10.1042/BST20230190. Online ahead of print.ABSTRACTThe genetic landscape of neurodegenerative diseases encompasses genes affecting multiple cellular pathways which exert effects in an array of neuronal and glial cell-types. Deconvolution of the roles of genes implicated in disease and the effects of disease-associated variants remains a vital step in the understanding of neurodegeneration and the development of therapeutics. Disease modelling using patient induced pluripotent stem cells (iPSCs) has enabled the generation of key cell-types associated with disease whilst maint...
Source: Biochemical Society Transactions - March 25, 2024 Category: Biochemistry Authors: Sarah N J Franks Rachel Heon-Roberts Brent J Ryan Source Type: research

Emerging mechanisms in the redox regulation of mitochondrial cytochrome c oxidase assembly and function
Biochem Soc Trans. 2024 Mar 25:BST20231183. doi: 10.1042/BST20231183. Online ahead of print.ABSTRACTIn eukaryotic cells, mitochondria perform cellular respiration through a series of redox reactions ultimately reducing molecular oxygen to water. The system responsible for this process is the respiratory chain or electron transport system (ETS) composed of complexes I-IV. Due to its function, the ETS is the main source of reactive oxygen species (ROS), generating them on both sides of the mitochondrial inner membrane, i.e. the intermembrane space (IMS) and the matrix. A correct balance between ROS generation and scavenging ...
Source: Biochemical Society Transactions - March 25, 2024 Category: Biochemistry Authors: Suleva Povea-Cabello Michele Brischigliaro Erika Fern ández-Vizarra Source Type: research

Scaffolds and the scaffolding domain: an alternative paradigm for caveolin-1 signaling
Biochem Soc Trans. 2024 Mar 25:BST20231570. doi: 10.1042/BST20231570. Online ahead of print.ABSTRACTCaveolin-1 (Cav1) is a 22 kDa intracellular protein that is the main protein constituent of bulb-shaped membrane invaginations known as caveolae. Cav1 can be also found in functional non-caveolar structures at the plasma membrane called scaffolds. Scaffolds were originally described as SDS-resistant oligomers composed of 10-15 Cav1 monomers observable as 8S complexes by sucrose velocity gradient centrifugation. Recently, cryoelectron microscopy (cryoEM) and super-resolution microscopy have shown that 8S complexes are interlo...
Source: Biochemical Society Transactions - March 25, 2024 Category: Biochemistry Authors: John E Lim Pascal Bernatchez Ivan R Nabi Source Type: research

A dynamic role for transcription factors in restoring transcription through mitosis
Biochem Soc Trans. 2024 Mar 25:BST20231022. doi: 10.1042/BST20231022. Online ahead of print.ABSTRACTMitosis involves intricate steps, such as DNA condensation, nuclear membrane disassembly, and phosphorylation cascades that temporarily halt gene transcription. Despite this disruption, daughter cells remarkably retain the parent cell's gene expression pattern, allowing for efficient transcriptional memory after division. Early studies in mammalian cells suggested that transcription factors (TFs) mark genes for swift reactivation, a phenomenon termed 'mitotic bookmarking', but conflicting data emerged regarding TF presence o...
Source: Biochemical Society Transactions - March 25, 2024 Category: Biochemistry Authors: Marek A Budzy ński Alexander K L Wong Armin Faghihi Sheila S Teves Source Type: research

Insights into the dynamics of the Ca2+ release-activated Ca2+ channel pore-forming complex Orai1
Biochem Soc Trans. 2024 Mar 25:BST20230815. doi: 10.1042/BST20230815. Online ahead of print.ABSTRACTAn important calcium (Ca2+) entry pathway into the cell is the Ca2+ release-activated Ca2+ (CRAC) channel, which controls a series of downstream signaling events such as gene transcription, secretion and proliferation. It is composed of a Ca2+ sensor in the endoplasmic reticulum (ER), the stromal interaction molecule (STIM), and the Ca2+ ion channel Orai in the plasma membrane (PM). Their activation is initiated by receptor-ligand binding at the PM, which triggers a signaling cascade within the cell that ultimately causes st...
Source: Biochemical Society Transactions - March 25, 2024 Category: Biochemistry Authors: Maximilian Fr öhlich Julia S öllner Isabella Derler Source Type: research

Complex I activity in hypoxia: implications for oncometabolism
Biochem Soc Trans. 2024 Mar 25:BST20230189. doi: 10.1042/BST20230189. Online ahead of print.ABSTRACTCertain cancer cells within solid tumors experience hypoxia, rendering them incapable of oxidative phosphorylation (OXPHOS). Despite this oxygen deficiency, these cells exhibit biochemical pathway activity that relies on NAD+. This mini-review scrutinizes the persistent, residual Complex I activity that oxidizes NADH in the absence of oxygen as the electron acceptor. The resulting NAD+ assumes a pivotal role in fueling the α-ketoglutarate dehydrogenase complex, a critical component in the oxidative decarboxylation branch of...
Source: Biochemical Society Transactions - March 25, 2024 Category: Biochemistry Authors: Christos Chinopoulos Source Type: research

CRISPRi: a way to integrate iPSC-derived neuronal models
Biochem Soc Trans. 2024 Mar 25:BST20230190. doi: 10.1042/BST20230190. Online ahead of print.ABSTRACTThe genetic landscape of neurodegenerative diseases encompasses genes affecting multiple cellular pathways which exert effects in an array of neuronal and glial cell-types. Deconvolution of the roles of genes implicated in disease and the effects of disease-associated variants remains a vital step in the understanding of neurodegeneration and the development of therapeutics. Disease modelling using patient induced pluripotent stem cells (iPSCs) has enabled the generation of key cell-types associated with disease whilst maint...
Source: Biochemical Society Transactions - March 25, 2024 Category: Biochemistry Authors: Sarah N J Franks Rachel Heon-Roberts Brent J Ryan Source Type: research

The role of lipids in genome integrity and pluripotency
Biochem Soc Trans. 2024 Mar 20:BST20230479. doi: 10.1042/BST20230479. Online ahead of print.ABSTRACTPluripotent stem cells (PSCs), comprising embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs), offer immense potential for regenerative medicine due to their ability to differentiate into all cell types of the adult body. A critical aspect of harnessing this potential is understanding their metabolic requirements during derivation, maintenance, and differentiation in vitro. Traditional culture methods using fetal bovine serum often lead to issues such as heterogeneous cell populations and diminished plurip...
Source: Biochemical Society Transactions - March 20, 2024 Category: Biochemistry Authors: Qiyu Tian Hoyoung Chung Duancheng Wen Source Type: research

The role of lipids in genome integrity and pluripotency
Biochem Soc Trans. 2024 Mar 20:BST20230479. doi: 10.1042/BST20230479. Online ahead of print.ABSTRACTPluripotent stem cells (PSCs), comprising embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs), offer immense potential for regenerative medicine due to their ability to differentiate into all cell types of the adult body. A critical aspect of harnessing this potential is understanding their metabolic requirements during derivation, maintenance, and differentiation in vitro. Traditional culture methods using fetal bovine serum often lead to issues such as heterogeneous cell populations and diminished plurip...
Source: Biochemical Society Transactions - March 20, 2024 Category: Biochemistry Authors: Qiyu Tian Hoyoung Chung Duancheng Wen Source Type: research

The role of lipids in genome integrity and pluripotency
Biochem Soc Trans. 2024 Mar 20:BST20230479. doi: 10.1042/BST20230479. Online ahead of print.ABSTRACTPluripotent stem cells (PSCs), comprising embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs), offer immense potential for regenerative medicine due to their ability to differentiate into all cell types of the adult body. A critical aspect of harnessing this potential is understanding their metabolic requirements during derivation, maintenance, and differentiation in vitro. Traditional culture methods using fetal bovine serum often lead to issues such as heterogeneous cell populations and diminished plurip...
Source: Biochemical Society Transactions - March 20, 2024 Category: Biochemistry Authors: Qiyu Tian Hoyoung Chung Duancheng Wen Source Type: research

The role of lipids in genome integrity and pluripotency
Biochem Soc Trans. 2024 Mar 20:BST20230479. doi: 10.1042/BST20230479. Online ahead of print.ABSTRACTPluripotent stem cells (PSCs), comprising embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs), offer immense potential for regenerative medicine due to their ability to differentiate into all cell types of the adult body. A critical aspect of harnessing this potential is understanding their metabolic requirements during derivation, maintenance, and differentiation in vitro. Traditional culture methods using fetal bovine serum often lead to issues such as heterogeneous cell populations and diminished plurip...
Source: Biochemical Society Transactions - March 20, 2024 Category: Biochemistry Authors: Qiyu Tian Hoyoung Chung Duancheng Wen Source Type: research

New insights into Gasdermin D pore formation
Biochem Soc Trans. 2024 Mar 18:BST20230549. doi: 10.1042/BST20230549. Online ahead of print.ABSTRACTGasdermin D (GSDMD) is a pore-forming protein that perforates the plasma membrane (PM) during pyroptosis, a pro-inflammatory form of cell death, to induce the unconventional secretion of inflammatory cytokines and, ultimately, cell lysis. GSDMD is activated by protease-mediated cleavage of its active N-terminal domain from the autoinhibitory C-terminal domain. Inflammatory caspase-1, -4/5 are the main activators of GSDMD via either the canonical or non-canonical pathways of inflammasome activation, but under certain stimuli,...
Source: Biochemical Society Transactions - March 18, 2024 Category: Biochemistry Authors: Shirin Kappelhoff Eleonora G Margheritis Katia Cosentino Source Type: research