Inhibition of nuclear deacetylase Sirtuin-1 induces mitochondrial acetylation and calcium overload leading to cell death

Sun, Yue; Yang, Yanming; Hu, Yu-Yu; Ouyang, Li; Sun, Zhi; Yin, Xinhua; Li, Nan; He, Qing-Yu; Wang, Yang

doi:10.1016/j.redox.2022.102334

Cited by 38 publications

(17 citation statements)

References 48 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Surgery‐related Ca 2+ overload in mitochondria is due to mitochondrial calcium uniporter (MCU, encoded by Micu1 ). Itpr1 could provide flow source by releasing calcium from ER, and Sirt1 could change acetylation levels of MCU and affect the calcium flow 52 . Previous study showed that both Ca 2+ efflux via Itpr1 and Ca 2+ influx via MCU promoted oxidative stress, 53 and led to membrane permeability increase, cytochrome c release, respiratory inhibition in neurons 54 .…”

Section: Discussionmentioning

confidence: 99%

Whole‐transcriptome sequencing identifies neuroinflammation, metabolism and blood–brain barrier related processes in the hippocampus of aged mice during perioperative period

et al. 2022

View full text Add to dashboard Cite

Aim: Perioperative neurocognitive disorders (PND) occur frequently after surgery and anesthesia, especially in aged patients. Previous studies have shown multiple PND related mechanisms in the hippocampus; however, their relationships remain unclear. Meanwhile, the perioperative neuropathological processes are sophisticated and changeable, single period study could not reveal the accurate mechanisms. Thus, multiperiod whole-transcriptome study is necessary to elucidate the gene expression patterns during perioperative period.Methods: Aged C57BL/6 mice were subjected to exploratory laparotomy under sevoflurane anesthesia. Whole-transcriptome sequencing (RNA-seq analysis) was performed on the hippocampi from control condition (Con), 30 min (Day0), 2 days (Day2), and 7 days (Day7) after surgery. Gene Ontology/Kyoto Encyclopedia of Genes and Genomes analyses, quantitative real-time PCR, immunofluorescence, and fear conditioning test were also performed to elucidate the pathological processes and modulation networks during the period.Results: Through RNA-seq analysis, 328, 3597, and 4179 differentially expressed genes (DEGs) were screened out in intraoperative period (Day0 vs. Con), early postoperative period (Day2 vs. Day0), and late postoperative period (Day7 vs. Day2). The involved GO biological processes were divided into 9 categories, and positive-regulated processes were more than negative-regulated ones. Seventy-four transcription factors were highlighted. The potential synaptic and neuroinflammatory pathways were constructed for Neurotransmitter, Synapse and Neuronal alteration categories with 9 genes (Htr1a, Rims1, and Ezh2, etc.). The metabolic and mitochondrial pathways were constructed for metabolism, oxidative stress, and biological rhythm categories with 9 genes (Gpld1, Sirt1, and Cry2, etc.). The blood-brain barrier and neurotoxicity related pathways were constructed for blood-brain barrier, neurotoxicity, and cognitive function categories with 10 genes (Mmp2, Itpr1, and Nrf1, etc.).

show abstract

Section: Discussionmentioning

confidence: 99%

Whole‐transcriptome sequencing identifies neuroinflammation, metabolism and blood–brain barrier related processes in the hippocampus of aged mice during perioperative period

et al. 2022

View full text Add to dashboard Cite

show abstract

“…hnRNPL loss has been associated with mitochondrial defects in fetal liver cells (Li et al , 2015; Gaudreau et al , 2016). SIRT1 is implicated in mitochondrial biogenesis and function, as well as mitophagy (Wan et al , 2022; Sun et al , 2022), partly by deacetylating PGC-1α and PGC-1β, transcriptional coactivators important for mitochondrial function (Kelly et al , 2009; Yi & Luo, 2010). GSEA analysis of DEG against a collection of metabolic and mitochondrial gene sets did not yield significant changes (not depicted).…”

Section: Resultsmentioning

confidence: 99%

“…Interestingly, mice lacking canonical autophagy in B cells have similar mitochondrial defects and fewer peripheral B cells (Arnold et al , 2016), likely because they fail to remove damaged and aged mitochondria (Pickles et al , 2018). Since hnRNPL-null B cells displayed splicing alterations in genes related to autophagy and reduced Sirt1, which also regulates mitophagy (Wan et al , 2022; Sun et al , 2022), it is conceivable that they have some autophagy defect and accumulate defective mitochondria. Alternatively, B cells that fail to receive a second signal following antigenic stimulation undergo activation-induced cell death via programmed mitochondrial dysfunction, showing reduced mitochondrial respiratory capacity despite increased MTG staining (Akkaya et al , 2018).…”

Section: Discussionmentioning

confidence: 99%

A conserved role of hnRNPL in regulating alternative splicing of transcriptional regulators necessary for B cell activation

Subramani,

Fraszczak,

Helness

et al. 2023

Preprint

View full text Add to dashboard Cite

The multifunctional RNA-binding protein hnRNPL has been implicated in antibody class switching but its broader function in B cells is unknown. Here, we show that hnRNPL is essential for B cell activation, and thereby germinal center and antibody responses. Upon activation, hnRNPL-deficient B cells show proliferation defects and increased apoptosis. Comparative analysis of RNA-seq data from activated B cells and another 8 hnRNPL-depleted cell types reveals a common function in the MYC and E2F transcriptional programs required for proliferation, likely borne out of alternative splicing changes affecting multiple transcription regulators. Notably, while individual gene expression changes were cell type specific, several alternative splicing events affecting histone modifiers like, KDM6A, NSD2, and SIRT1, were conserved across cell types, which could contribute to gene expression changes and other phenotypes upon hnRNPL loss. In line with reduced SIRT1, hnRNPL-deficient B cells had dysfunctional mitochondria and ROS overproduction, which could contribute to defects in B cell activation. Thus, hnRNPL is essential for the resting-to-activated B cell transition by regulating transcriptional programs and metabolism, most likely through the alternative splicing of several histone modifiers.

show abstract

“…Mitochondria are highly dynamic organelles in mammalian cells that play critical roles in energy production (Sun et al , 2022). As a hallmark of cancer, abnormality in mitochondrial energy metabolism predominately contributes to the pathogenesis of ccRCC.…”

Section: Discussionmentioning

confidence: 99%

LINC00493‐encoded microprotein SMIM26 exerts anti‐metastatic activity in renal cell carcinoma

Meng

et al. 2023

EMBO Reports

Self Cite

View full text Add to dashboard Cite

Human microproteins encoded by long non‐coding RNAs (lncRNA) have been increasingly discovered, however, complete functional characterization of these emerging proteins is scattered. Here, we show that LINC00493‐encoded SMIM26, an understudied microprotein localized in mitochondria, is tendentiously downregulated in clear cell renal cell carcinoma (ccRCC) and correlated with poor overall survival. LINC00493 is recognized by RNA‐binding protein PABPC4 and transferred to ribosomes for translation of a 95‐amino‐acid protein SMIM26. SMIM26, but not LINC00493, suppresses ccRCC growth and metastatic lung colonization by interacting with acylglycerol kinase (AGK) and glutathione transport regulator SLC25A11 via its N‐terminus. This interaction increases the mitochondrial localization of AGK and subsequently inhibits AGK‐mediated AKT phosphorylation. Moreover, the formation of the SMIM26‐AGK‐SCL25A11 complex maintains mitochondrial glutathione import and respiratory efficiency, which is abrogated by AGK overexpression or SLC25A11 knockdown. This study functionally characterizes the LINC00493‐encoded microprotein SMIM26 and establishes its anti‐metastatic role in ccRCC, and therefore illuminates the importance of hidden proteins in human cancers.

show abstract

Inhibition of nuclear deacetylase Sirtuin-1 induces mitochondrial acetylation and calcium overload leading to cell death

Cited by 38 publications

References 48 publications

Whole‐transcriptome sequencing identifies neuroinflammation, metabolism and blood–brain barrier related processes in the hippocampus of aged mice during perioperative period

Whole‐transcriptome sequencing identifies neuroinflammation, metabolism and blood–brain barrier related processes in the hippocampus of aged mice during perioperative period

A conserved role of hnRNPL in regulating alternative splicing of transcriptional regulators necessary for B cell activation

LINC00493‐encoded microprotein SMIM26 exerts anti‐metastatic activity in renal cell carcinoma

Contact Info

Product

Resources

About