bims-cesemi Biomed News
on Cellular senescence and mitochondria
Issue of 2024–09–08
seventeen papers selected by
Julio Cesar Cardenas, Universidad Mayor
  1. Senolytics target cellular senescence - but can they slow aging?
  2. Mitochondria-Associated Membranes in Aging and Senescence.
  3. Cellular senescence exacerbates features of aging in the eyes.
  4. Cellular Senescence in Diffuse Gliomas: From Physiopathology to Possible Treatments.
  5. Deoxyarbutin targets mitochondria to trigger p53-dependent senescence of glioblastoma cells.
  6. Topical ABT-263 treatment reduces aged skin senescence and improves subsequent wound healing.
  7. Ribosomal S6 kinase 1 regulates inflammaging via the senescence secretome.
  8. Considering the Future of Geroscience: Goals and Opportunities Stemming From the Fourth Geroscience Summit.
  9. Defying "IL-11ness" by inhibiting inflammation: Strategy for health and longevity.
  10. Gut-muscle axis mechanism of exercise prevention of sarcopenia.
  11. Mitochondrial transplants to treat mitochondrial dysfunction.
  12. Mitochondrial Adaptations in Aging Skeletal Muscle: Implications for Resistance Exercise Training to Treat Sarcopenia.
  13. Promotion of endoplasmic reticulum retrotranslocation by overexpression of E3 ubiquitin-protein ligase synoviolin 1 reduces endoplasmic reticulum stress and preserves cone photoreceptors in cyclic nucleotide-gated channel deficiency.
  14. A 2-hydroxybutyrate-mediated feedback loop regulates muscular fatigue.
  15. Senescent cell clearance ameliorates temporal lobe epilepsy and associated spatial memory deficits in mice.
  16. The Effects of Ketogenic Diets and Ketone Supplements on the Aerobic Performance of Endurance Runners: A Systematic Review.
  17. Direct measurements of luminal Ca 2+ with endo-lysosomal GFP-aequorin reveal functional IP 3 receptors.
  1. Nat Med. 2024 Sep 02.
    Senolytics target cellular senescence - but can they slow aging?
    Natalie Healey.
      
    DOI:  https://doi.org/10.1038/d41591-024-00067-5
  2. Aging Dis. 2024 Aug 22.
    Mitochondria-Associated Membranes in Aging and Senescence.
    Zhaojia Wang, Xiao Du, Shiran Yu, Xuzhen Yan, Yanguo Xin.
      Although the pursuit of eternal youth remains elusive, progress in the fields of medicine and science has greatly extended the human lifespan. Nevertheless, the rising incidence of diseases and their economic impact present notable obstacles. Mitochondria-associated membranes (MAMs), essential sites for close interaction between mitochondria and the endoplasmic reticulum (ER), are increasingly recognized for their involvement in both normal cellular processes and the development of diseases. Studies suggest that MAMs undergo dynamic alterations, particularly pertinent in the investigation of age-related illnesses. This review highlights the significance of MAMs in age-related conditions, elucidating the morphological and functional alterations in mitochondria and ER during aging. By emphasizing the complex interaction between these organelles, it demonstrates the cell's adaptive responses to combat age-related deterioration. Suggesting MAMs as potential targets for therapeutic interventions holds the potential for attenuating the progression of age-related diseases.
    DOI:  https://doi.org/10.14336/AD.2024.0652
  3. Aging Biol. 2023 ;pii: 20230014. [Epub ahead of print]1(1):
    Cellular senescence exacerbates features of aging in the eyes.
    Koji Kitazawa, Kohsaku Numa, Sandip Kumar Patel, Christina D King, Akifumi Matsumoto, Chie Sotozono, Pierre-Yves Desprez, Birgit Schilling, Judith Campisi.
      Aging is a process often associated with various age-related diseases. Senescence is one of the hallmarks of aging, and senescent cells acquire a complex, often pro-inflammatory, secretory phenotype termed the senescence-associated secretory phenotype (SASP). Here we show that ocular surface cells from human cornea become senescent upon X-irradiation, characterized by increased SA-β-gal activity, decreased cell proliferation, increased expression of p16, and disruption of epithelial barrier. Comprehensive transcriptomic and proteomic analysis revealed that human senescent ocular cells acquire a SASP that disrupts epithelial barrier function. During aging in mice, senescent ocular cells accumulate, resulting in decreased epithelial barrier and chronic inflammation. Lacrimal gland excision, which leads to symptoms of dry eye (DE), resulted in corneal opacity associated with severe angiogenesis only in aged mice but not in young mice, and early senolytic treatment protected old DE mice from corneal opacity. In conclusion, senescent cells alter the ocular microenvironment through their SASP and eliminating these cells could represent a potential approach to alleviate symptoms associated with aged ocular surface.
    Keywords:  dry eye; lacrimal gland excision; mouse models; ocular surface; proteomics; senescence-associated secretory phenotype
    DOI:  https://doi.org/10.59368/agingbio.20230014
  4. World Neurosurg. 2024 Sep 02. pii: S1878-8750(24)01428-1. [Epub ahead of print]
    Cellular Senescence in Diffuse Gliomas: From Physiopathology to Possible Treatments.
    Edgar G Ordóñez-Rubiano, Alba Cómbita, Matías Baldoncini, César Payán-Gómez, Diego F Gómez-Amarillo, Fernando Hakim, Julián Camargo, Valentina Zorro-Sepúlveda, Sabino Luzzi, Oscar Zorro, Rafael Parra- Medina.
      Cellular senescence in gliomas is a complex process that is induced by aging and replication, ionizing radiation, oncogenic stress, and the use of temozolomide. However, the escape routes that gliomas must evade senescence and achieve cellular immortality are much more complex, in which the expression of telomerase and the alternative lengthening of telomeres, as well as the mutation of some proto-oncogenes or tumor suppressor genes, are involved. In gliomas, these molecular mechanisms related to cellular senescence can have a tumor-suppressing or promoting effect and are directly involved in tumor recurrence and progression. From these cellular mechanisms related to cellular senescence, it is possible to generate targeted senostatic and senolytic therapies that improve the response to currently available treatments and improve survival rates. This review aims to summarize the mechanisms of induction and evasion of cellular senescence in gliomas, as well as review possible treatments with therapies targeting pathways related to cellular senescence.
    Keywords:  cellular senescence; diffuse glioma; glioblastoma; glioma; molecular pathology; senescence
    DOI:  https://doi.org/10.1016/j.wneu.2024.08.060
  5. Free Radic Biol Med. 2024 Aug 27. pii: S0891-5849(24)00621-X. [Epub ahead of print]
    Deoxyarbutin targets mitochondria to trigger p53-dependent senescence of glioblastoma cells.
    Dongjing Cai, Xia Xu, Weiqian Zeng, Zheng Wang, Cheng Chen, Yunan Mo, Piyanat Meekrathok, Dandan Wang, Pengwei Peng, Zhigang Peng, Jian Qiu.
      Cellular senescence is a natural barrier of the transition from premalignant cells to invasive cancer. Pharmacological induction of senescence has been proposed as a possible anticancer strategy. In this study, we found that deoxyarbutin inhibited the growth of glioblastoma (GBM) cells by inducing cellular senescence, independent of tyrosinase expression. Instead, deoxyarbutin induced mitochondrial oxidative stress and damage. These aberrant mitochondria were key to the p53-dependent senescence of GBM cells. Facilitating autophagy or mitigating mitochondrial oxidative stress both suppressed p53 expression and alleviated cellular senescence induced by deoxyarbutin. Thus, our study reveals that deoxyarbutin induces mitochondrial oxidative stress to trigger the p53-dependent senescence of GBM cells. Importantly, deoxyarbutin treatment resulted in accumulation of p53, induction of cellular senescence, and inhibition of tumor growth in a subcutaneous tumor model of mouse. In conclusion, our study reveals that deoxyarbutin has therapeutic potential for GBM by inducing mitochondrial oxidative stress for p53-dependent senescence of GBM cells.
    Keywords:  deoxyarbutin; glioblastoma; mitochondria; p53; senescence
    DOI:  https://doi.org/10.1016/j.freeradbiomed.2024.08.027
  6. bioRxiv. 2024 Aug 20. pii: 2024.08.19.608670. [Epub ahead of print]
    Topical ABT-263 treatment reduces aged skin senescence and improves subsequent wound healing.
    Maria Shvedova, Rex Jeya Rajkumar Samdavid Thanapaul, Joy Ha, Jannat Dhillon, Grace H Shin, Jack Crouch, Adam C Gower, Sami Gritli, Daniel S Roh.
      Senescent cells (SnC) accumulate in aging tissues, impairing their ability to undergo repair and regeneration following injury. Previous research has demonstrated that targeting tissue senescence with senolytics can enhance tissue regeneration and repair by selectively eliminating SnCs in specific aged tissues. In this study, we focused on eliminating SnC skin cells in aged mice to assess the effects on subsequent wound healing. We applied ABT-263 directly to the skin of 24-month-old mice over a 5-day period. Following topical ABT-263, aged skin demonstrated decreased gene expression of senescent markers p16 and p21, accompanied by reductions in SA-β-gal and p21-positive cells compared to DMSO controls. However, ABT-263 also triggered a temporary inflammatory response and macrophage infiltration in the skin. Bulk RNA sequencing of ABT-263-treated skin revealed prompt upregulation of genes associated with wound healing pathways, including hemostasis, inflammation, cell proliferation, angiogenesis, collagen synthesis, and extracellular matrix organization. Aged mice skin pre-treated with topical ABT-263 exhibited accelerated wound closure. In conclusion, topical ABT-263 effectively reduced several senescence markers in aged skin, thereby priming the skin for improved subsequent wound healing. This enhancement may be attributed to ABT-263-induced senolysis which in turn stimulates the expression of genes involved in extracellular matrix remodeling and wound repair pathways.
    DOI:  https://doi.org/10.1101/2024.08.19.608670
  7. Nat Aging. 2024 Aug 29.
    Ribosomal S6 kinase 1 regulates inflammaging via the senescence secretome.
    Suchira Gallage, Elaine E Irvine, Jose Efren Barragan Avila, Virinder Reen, Silvia M A Pedroni, Imanol Duran, Vikas Ranvir, Sanjay Khadayate, Joaquim Pombo, Sharon Brookes, Danijela Heide, Gopuraja Dharmalingham, Agharul I Choudhury, Indrabahadur Singh, Nicolás Herranz, Santiago Vernia, Mathias Heikenwalder, Jesús Gil, Dominic J Withers.
      Inhibition of S6 kinase 1 (S6K1) extends lifespan and improves healthspan in mice, but the underlying mechanisms are unclear. Cellular senescence is a stable growth arrest accompanied by an inflammatory senescence-associated secretory phenotype (SASP). Cellular senescence and SASP-mediated chronic inflammation contribute to age-related pathology, but the specific role of S6K1 has not been determined. Here we show that S6K1 deletion does not reduce senescence but ameliorates inflammation in aged mouse livers. Using human and mouse models of senescence, we demonstrate that reduced inflammation is a liver-intrinsic effect associated with S6K deletion. Specifically, we show that S6K1 deletion results in reduced IRF3 activation; impaired production of cytokines, such as IL1β; and reduced immune infiltration. Using either liver-specific or myeloid-specific S6K knockout mice, we also demonstrate that reduced immune infiltration and clearance of senescent cells is a hepatocyte-intrinsic phenomenon. Overall, deletion of S6K reduces inflammation in the liver, suggesting that suppression of the inflammatory SASP by loss of S6K could underlie the beneficial effects of inhibiting this pathway on healthspan and lifespan.
    DOI:  https://doi.org/10.1038/s43587-024-00695-z
  8. J Gerontol A Biol Sci Med Sci. 2024 Sep 01. pii: glae179. [Epub ahead of print]79(9):
    Considering the Future of Geroscience: Goals and Opportunities Stemming From the Fourth Geroscience Summit.
    Siobhan Addie, Ronald Kohanski, Luigi Ferrucci, Christy Carter, Stacy Carrington-Lawrence.
      
    DOI:  https://doi.org/10.1093/gerona/glae179
  9. Cell Metab. 2024 Sep 03. pii: S1550-4131(24)00330-9. [Epub ahead of print]36(9): 1911-1913
    Defying "IL-11ness" by inhibiting inflammation: Strategy for health and longevity.
    Hee-Hoon Kim, Vishwa Deep Dixit.
      Organismal aging involves several hallmark pathways, including chronic inflammation and metabolic dysfunction. However, the origin of age-related inflammation is incompletely understood. In a recent study published in Nature,1 Widjaja et al. show that blocking the age-related increase in IL-11 restores immune-metabolic homeostasis and extends healthspan and lifespan in mice.
    DOI:  https://doi.org/10.1016/j.cmet.2024.08.003
  10. Front Nutr. 2024 ;11 1418778
    Gut-muscle axis mechanism of exercise prevention of sarcopenia.
    Tao Li, Danyang Yin, Rengfei Shi.
      Sarcopenia refers to an age-related systemic skeletal muscle disorder, which is characterized by loss of muscle mass and weakening of muscle strength. Gut microbiota can affect skeletal muscle through a variety of mechanisms. Gut microbiota present distinct features among elderly people and sarcopenia patients, including a decrease in microbial diversity, which might be associated with the quality and function of the skeletal muscle. There might be a gut-muscle axis; where gut microbiota and skeletal muscle may affect each other bi-directionally. Skeletal muscle can affect the biodiversity of the gut microbiota, and the latter can, in turn, affect the anabolism of skeletal muscle. This review examines recent studies exploring the relationship between gut microbiota and skeletal muscle, summarizes the effects of exercise on gut microbiota, and discusses the possible mechanisms of the gut-muscle axis.
    Keywords:  SCFAs; exercise; gut microbiota; gut-muscle axis; sarcopenia
    DOI:  https://doi.org/10.3389/fnut.2024.1418778
  11. Nat Metab. 2024 Sep 02.
    Mitochondrial transplants to treat mitochondrial dysfunction.
    Alessandro Bitto.
      
    DOI:  https://doi.org/10.1038/s42255-024-01124-6
  12. Life (Basel). 2024 Jul 31. pii: 962. [Epub ahead of print]14(8):
    Mitochondrial Adaptations in Aging Skeletal Muscle: Implications for Resistance Exercise Training to Treat Sarcopenia.
    Ilyoung Jeong, Eun-Jeong Cho, Jang-Soo Yook, Youngju Choi, Dong-Ho Park, Ju-Hee Kang, Seok-Hun Lee, Dae-Yun Seo, Su-Jeen Jung, Hyo-Bum Kwak.
      Sarcopenia, the age-related decline in muscle mass and function, poses a significant health challenge as the global population ages. Mitochondrial dysfunction is a key factor in sarcopenia, as evidenced by the role of mitochondrial reactive oxygen species (mtROS) in mitochondrial biogenesis and dynamics, as well as mitophagy. Resistance exercise training (RET) is a well-established intervention for sarcopenia; however, its effects on the mitochondria in aging skeletal muscles remain unclear. This review aims to elucidate the relationship between mitochondrial dynamics and sarcopenia, with a specific focus on the implications of RET. Although aerobic exercise training (AET) has traditionally been viewed as more effective for mitochondrial enhancement, emerging evidence suggests that RET may also confer beneficial effects. Here, we highlight the potential of RET to modulate mtROS, drive mitochondrial biogenesis, optimize mitochondrial dynamics, and promote mitophagy in aging skeletal muscles. Understanding this interplay offers insights for combating sarcopenia and preserving skeletal muscle health in aging individuals.
    Keywords:  aging; mitochondria; resistance exercise training; sarcopenia; skeletal muscle
    DOI:  https://doi.org/10.3390/life14080962
  13. FASEB J. 2024 Sep 15. 38(17): e70021
    Promotion of endoplasmic reticulum retrotranslocation by overexpression of E3 ubiquitin-protein ligase synoviolin 1 reduces endoplasmic reticulum stress and preserves cone photoreceptors in cyclic nucleotide-gated channel deficiency.
    Fan Yang, Hongwei Ma, Sanford L Boye, Shannon E Boye, Xi-Qin Ding.
      Cone photoreceptor cyclic nucleotide-gated (CNG) channels play an essential role in phototransduction and cellular Ca2+ homeostasis. Mutations in genes encoding the channel subunits CNGA3 and CNGB3 are associated with achromatopsia, progressive cone dystrophy, and early-onset macular degeneration. Cone loss in patients with achromatopsia and cone dystrophy associated with CNG channel mutations has been documented by optical coherence tomography and in mouse models of CNG channel deficiency. Cone death in CNG channel-deficient retinas involves endoplasmic reticulum (ER) stress-associated apoptosis, dysregulation of cellular/ER Ca2+ homeostasis, impaired protein folding/processing, and impaired ER-associated degradation (ERAD). The E3 ubiquitin-protein ligase synoviolin 1 (SYVN1) is the primary component of the SYVN1/SEL1L ER retrotranslocon responsible for ERAD. Previous studies have shown that manipulations that protect cones and reduce ER stress/cone death in CNG channel deficiency, such as increasing ER Ca2+ preservation or treatment with an ER chaperone, increase the expression of SYVN1 and other components of the ER retrotranslocon. The present work investigated the effects of SYVN1 overexpression. Intraocular injection of AAV5-IRBP/GNAT2-Syvn1 resulted in overexpression of SYVN1 in cones of CNG channel-deficient mice. Following treatment, cone density in Cnga3-/- mice was significantly increased, compared with untreated controls, outer segment localization of cone opsin was improved, and ER stress/apoptotic cell death was reduced. Overexpression of SYVN1 also led to increased expression levels of the retrotranslocon components, degradation in ER protein 1 (DERL1), ERAD E3 ligase adaptor subunit (SEL1L), and homocysteine inducible ER protein with ubiquitin-like domain 1 (HERPUD1). Moreover, overexpression of SYVN1 likely enhanced protein ubiquitination/proteasome degradation in CNG channel-deficient retinas. This study demonstrates the role of SYVN1/ERAD in cone preservation in CNG channel deficiency and supports the strategy of promoting ERAD for cone protection.
    Keywords:  CNG channel; ER stress; ERAD; SYVN1; cone photoreceptors; retinal degeneration
    DOI:  https://doi.org/10.1096/fj.202400198R
  14. Elife. 2024 Sep 03. pii: RP92707. [Epub ahead of print]12
    A 2-hydroxybutyrate-mediated feedback loop regulates muscular fatigue.
    Brennan J Wadsworth, Marina Leiwe, Eleanor A Minogue, Pedro P Cunha, Viktor Engman, Carolin Brombach, Christos Asvestis, Shiv K Sah-Teli, Emilia Marklund, Peppi Karppinen, Jorge L Ruas, Helene Rundqvist, Johanna T Lanner, Randall S Johnson.
      Several metabolites have been shown to have independent and at times unexpected biological effects outside of their metabolic pathways. These include succinate, lactate, fumarate, and 2-hydroxyglutarate. 2-Hydroxybutyrate (2HB) is a byproduct of endogenous cysteine synthesis, produced during periods of cellular stress. 2HB rises acutely after exercise; it also rises during infection and is also chronically increased in a number of metabolic disorders. We show here that 2HB inhibits branched-chain aminotransferase enzymes, which in turn triggers a SIRT4-dependent shift in the compartmental abundance of protein ADP-ribosylation. The 2HB-induced decrease in nuclear protein ADP-ribosylation leads to a C/EBPβ-mediated transcriptional response in the branched-chain amino acid degradation pathway. This response to 2HB exposure leads to an improved oxidative capacity in vitro. We found that repeated injection with 2HB can replicate the improvement to oxidative capacity that occurs following exercise training. Together, we show that 2-HB regulates fundamental aspects of skeletal muscle metabolism.
    Keywords:  Exercise; biochemistry; chemical biology; metabolite; mouse; muscle fiber
    DOI:  https://doi.org/10.7554/eLife.92707
  15. bioRxiv. 2024 Jul 31. pii: 2024.07.30.605784. [Epub ahead of print]
    Senescent cell clearance ameliorates temporal lobe epilepsy and associated spatial memory deficits in mice.
    Tahiyana Khan, David J McFall, Abbas I Hussain, Logan A Frayser, Timothy P Casilli, Meaghan C Steck, Irene Sanchez-Brualla, Noah M Kuehn, Michelle Cho, Jacqueline A Barnes, Brent T Harris, Stefano Vicini, Patrick A Forcelli.
      Current therapies for the epilepsies only treat the symptoms, but do not prevent epileptogenesis (the process in which epilepsy develops). Many cellular responses during epileptogenesis are also common hallmarks of cellular senescence , which halts proliferation of damaged cells. Clearing senescent cells (SCs) restores function in several age-associated and neurodegenerative disease models. It is unknown whether SC accumulation contributes to epileptogenesis and associated cognitive impairments. To address this question, we used a mouse model of temporal lobe epilepsy (TLE) and characterized the senescence phenotype throughout epileptogenesis. SCs accumulated 2 weeks after SE and were predominantly microglia. We ablated SCs and reduced (and in some cases prevented) the emergence of spontaneous seizures and normalized cognitive function in mice. Suggesting that this is a translationally-relevant target we also found SC accumulation in resected hippocampi from patients with TLE. These findings indicate that SC ablation after an epileptogenic insult is a potential anti-epileptogenic therapy.
    DOI:  https://doi.org/10.1101/2024.07.30.605784
  16. Sports Health. 2024 Sep 04. 19417381241271547
    The Effects of Ketogenic Diets and Ketone Supplements on the Aerobic Performance of Endurance Runners: A Systematic Review.
    Kexin Sun, Yee Tung Choi, Clare Chung Wah Yu, Edmund Anthony Severn Nelson, Jorming Goh, Siyu Dai, Lai Ling Hui.
       CONTEXT: Ketogenic diets and ketone supplements have gained popularity among endurance runners given their purported effects: potentially delaying the onset of fatigue by enabling the increased utilization of the body's fat reserve or external ketone bodies during prolonged running.
    OBJECTIVE: This systematic review was conducted to evaluate the effects of ketogenic diets (>60% fat and <10% carbohydrates/<50 g carbohydrates per day) or ketone supplements (ketone esters or ketone salts, medium-chain triglycerides or 1,3-butadiol) on the aerobic performance of endurance runners.
    DATA SOURCES: A systematic search was conducted in PubMed, Web of Science, Pro Quest, and Science Direct for publications up to October 2023.
    STUDY SELECTION: Human studies on the effects of ketogenic diets or ketone supplements on the aerobic performance of adult endurance runners were included after independent screening by 2 reviewers.
    STUDY DESIGN: Systematic review.
    LEVEL OF EVIDENCE: Level 3.
    DATA EXTRACTION: Primary outcomes were markers of aerobic performance (maximal oxygen uptake [VO2max], race time, time to exhaustion and rate of perceived exertion).
    RESULTS: VO2max was assessed by incremental test to exhaustion. Endurance performance was assessed by time trials, 180-minute running trials, or run-to-exhaustion trials; 5 studies on ketogenic diets and 7 studies on ketone supplements involving a total of 132 endurance runners were included. Despite the heterogeneity in study design and protocol, none reported benefits of ketogenic diets or ketone supplements on selected markers of aerobic performance compared with controls. Reduction in bodyweight and fat while preserving lean mass and improved glycemic control were reported in some included studies on ketogenic diets.
    CONCLUSION: This review did not identify any significant advantages or disadvantages of ketogenic diets or ketone supplements for the aerobic performance of endurance runners. Further trials with larger sample sizes, more gender-balanced participants, longer ketogenic diet interventions, and follow-up on metabolic health are warranted.
    Keywords:  aerobic performance; endurance runners; ketogenic diets; ketone supplements
    DOI:  https://doi.org/10.1177/19417381241271547
  17. bioRxiv. 2024 Jul 26. pii: 2023.07.11.547422. [Epub ahead of print]
    Direct measurements of luminal Ca 2+ with endo-lysosomal GFP-aequorin reveal functional IP 3 receptors.
    B Calvo, P Torres-Vidal, A Delrio-Lorenzo, C Rodriguez, F J Aulestia, J Rojo-Ruiz, B M McVeigh, V Moiseenkova-Bell, D I Yule, J Garcia-Sancho, S Patel, M T Alonso.
      Endo-lysosomes are considered acidic Ca 2+ stores but direct measurements of luminal Ca 2+ within them are limited. Here we report that the Ca 2+ -sensitive luminescent protein aequorin does not reconstitute with its cofactor at highly acidic pH but that a significant fraction of the probe is functional within a mildly acidic compartment when targeted to the endo-lysosomal system. We leveraged this probe (ELGA) to report Ca 2+ dynamics in this compartment. We show that Ca 2+ uptake is ATP-dependent and sensitive to blockers of endoplasmic reticulum Ca 2+ pumps. We find that the Ca 2+ mobilizing messenger IP 3 which typically targets the endoplasmic reticulum evokes robust luminal responses in wild type cells, but not in IP 3 receptor knock-out cells. Responses were comparable to those evoked by activation of the endo-lysosomal ion channel TRPML1. Stimulation with IP 3 -forming agonists also mobilized the store in intact cells. Super-resolution microscopy analysis confirmed the presence of IP 3 receptors within the endo-lysosomal system, both in live and fixed cells. Our data reveal a physiologically-relevant, IP 3 -sensitive store of Ca 2+ within the endo-lysosomal system.
    DOI:  https://doi.org/10.1101/2023.07.11.547422
This page is being maintained by Thomas Krichel. It was last updated on 2024‒11‒22 at 4:13.