Lysosome signaling in cell survival and programmed cell death for cellular homeostasis

Patra, Srimanta; Patil, Shankargouda; Klionsky, Daniel J.; Bhutia, Sujit K.

doi:10.1002/jcp.30928

Cited by 29 publications

(18 citation statements)

References 183 publications

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“…PCD is an active cell death mode mediated by speci c genes and proteins, which has an essential role in maintaining the growth and development of the body and the normal physiological functions of tissues and organs [35]. The PCD reported in KIRC are ferroptosis, autophagy, apoptosis, etc.…”

Section: Discussionmentioning

confidence: 99%

Construction of five disulfidptosis-related lncRNA signature for predicting prognosis and immune activity in kidney renal clear cell carcinoma

Zhang

et al. 2023

Preprint

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Kidney renal clear cell carcinoma (KIRC) is a highly aggressive cancer. Disulfidptosis is a newly discovered mechanism of programmed cell death. However, the role of disulfidptosis-related lncRNAs (DRlncRNAs) in KIRC remains unknown. This study aimed to develop a prognostic model of DRlncRNAs and explore their prognostic value in KIRC. RNA-seq and relevant clinical data were obtained from The Cancer Genome Atlas (TCGA) database. Univariate Cox regression, lasso algorithm and multivariate Cox regression analysis identified DRlncRNAs and established a prognostic model. Multiple methods to assess the reliability of the model. In addition, Gene Set Enrichment Analysis (GSEA), immune infiltration analysis, somatic mutation analysis, and drug prediction were performed on the model. qRT-PCR has identified the intracellular expression of DRlncRNAs. We constructed a prognostic model with five DRlncRNAs and proved that the model was a good predictor of survival and prognosis of KIRC patients. GSEA indicated that DRlncRNAs were associated with apoptosis and immune-related pathways. Immune correlation analysis suggested that low-risk patients had better immunotherapeutic outcomes. Besides, somatic mutation analysis revealed that low-risk patients had a lower somatic mutation rate and TMB score and better prognostic. Drug prediction showed that axitinib, ibrutinib, osimertinib, and ruxolitinib were more effective in the low-risk patients; Crizotinib, lapatinib, linsitinib, and nilotinib were more effective in the high-risk patients. Finally, qRT-PCR confirmed the expression of DRlncRNAs in normal kidney cells and KIRC cell lines. In summary, we constructed a risk model and provided a new direction for diagnosing and treating KIRC.

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Section: Discussionmentioning

confidence: 99%

Construction of five disulfidptosis-related lncRNA signature for predicting prognosis and immune activity in kidney renal clear cell carcinoma

Zhang

et al. 2023

Preprint

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“…Autophagy is a major intracellular degradation process in which autophagosomes sequester cytoplasmic components such as damaged proteins and intracellular organelles and then fuse with lysosomes to degrade those cytoplasmic components. The intracellular organelles in which autophagosomes and lysosomes are fused together are called autolysosomes [ 87 ]. The mechanistic (or mammalian) target of rapamycin complex 1 (mTORC1) is the key regulator of the initiation phase of autophagy, although numerous other molecules, such as microtubule-associated protein 1 light chain 3 (LC3), are also involved in autophagy.…”

Section: Bas As Regulatory Modulatorsmentioning

confidence: 99%

Role of Microbiota-Modified Bile Acids in the Regulation of Intracellular Organelles and Neurodegenerative Diseases

Kiriyama

Nochi

2023

Genes

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Bile acids (BAs) are amphiphilic steroidal molecules generated from cholesterol in the liver and facilitate the digestion and absorption of fat-soluble substances in the gut. Some BAs in the intestine are modified by the gut microbiota. Because BAs are modified in a variety of ways by different types of bacteria present in the gut microbiota, changes in the gut microbiota can affect the metabolism of BAs in the host. Although most BAs absorbed from the gut are transferred to the liver, some are transferred to the systemic circulation. Furthermore, BAs have also been detected in the brain and are thought to migrate into the brain through the systemic circulation. Although BAs are known to affect a variety of physiological functions by acting as ligands for various nuclear and cell-surface receptors, BAs have also been found to act on mitochondria and autophagy in the cell. This review focuses on the BAs modified by the gut microbiota and their roles in intracellular organelles and neurodegenerative diseases.

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“…Lysosomes are membrane-bound cytoplasmic organelles equipped with acid hydrolases whose major function consists in preserving cellular homeostasis by breaking down cellular (organized in autophagosomes) and extracellular (imported with endosomes) macromolecules and organelles into their fundamental components [ 19 , 20 ]. Lysosomal storage diseases (LSDs) are inborn metabolism defects often caused by loss-of-function (LOF) mutations in genes encoding lysosomal hydrolases.…”

Section: Introductionmentioning

confidence: 99%

Genetic Evidence for Endolysosomal Dysfunction in Parkinson’s Disease: A Critical Overview

Yahya

Fonzo

Monfrini

2023

IJMS

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Parkinson’s disease (PD) is the second most common neurodegenerative disorder in the aging population, and no disease-modifying therapy has been approved to date. The pathogenesis of PD has been related to many dysfunctional cellular mechanisms, however, most of its monogenic forms are caused by pathogenic variants in genes involved in endolysosomal function (LRRK2, VPS35, VPS13C, and ATP13A2) and synaptic vesicle trafficking (SNCA, RAB39B, SYNJ1, and DNAJC6). Moreover, an extensive search for PD risk variants revealed strong risk variants in several lysosomal genes (e.g., GBA1, SMPD1, TMEM175, and SCARB2) highlighting the key role of lysosomal dysfunction in PD pathogenesis. Furthermore, large genetic studies revealed that PD status is associated with the overall “lysosomal genetic burden”, namely the cumulative effect of strong and weak risk variants affecting lysosomal genes. In this context, understanding the complex mechanisms of impaired vesicular trafficking and dysfunctional endolysosomes in dopaminergic neurons of PD patients is a fundamental step to identifying precise therapeutic targets and developing effective drugs to modify the neurodegenerative process in PD.

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Lysosome signaling in cell survival and programmed cell death for cellular homeostasis

Cited by 29 publications

References 183 publications

Construction of five disulfidptosis-related lncRNA signature for predicting prognosis and immune activity in kidney renal clear cell carcinoma

Construction of five disulfidptosis-related lncRNA signature for predicting prognosis and immune activity in kidney renal clear cell carcinoma

Role of Microbiota-Modified Bile Acids in the Regulation of Intracellular Organelles and Neurodegenerative Diseases

Genetic Evidence for Endolysosomal Dysfunction in Parkinson’s Disease: A Critical Overview

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