bims-cesemi Biomed News
on Cellular senescence and mitochondria
Issue of 2026–06–28
eight papers selected by
Julio Cesar Cardenas, Universidad Mayor
  1. Mitochondria-endoplasmic reticulum contact sites as hubs where mitochondria acquire iron.
  2. PIGBOS-CLCC1 interaction shapes cellular calcium dynamics and energy metabolism.
  3. The multifaceted inducers of cellular senescence.
  4. Horizontal mitochondrial transfer and the tug-of-war between cancer cells and immune cells.
  5. Mitochondrial Ca2+ signaling: A metabolic rheostat defining tumor and immune cell fate.
  6. MitoCatch directs mitochondria delivery and prevents cell degeneration.
  7. PIKfyve influences inter-organelle contacts with lysosomes to modulate the endoplasmic reticulum.
  8. A ratiometric fluorescent reporter of mitochondrial sodium.
  1. Nat Cell Biol. 2026 Jun 26.
    Mitochondria-endoplasmic reticulum contact sites as hubs where mitochondria acquire iron.
      
    DOI:  https://doi.org/10.1038/s41556-026-02008-5
  2. Cell Commun Signal. 2026 Jun 25.
    PIGBOS-CLCC1 interaction shapes cellular calcium dynamics and energy metabolism.
    Seemanti Aditya, Amal Kanti Bera.
      PIGBOS is a recently identified 54-amino acid microprotein localized to the mitochondrial outer membrane and implicated in the endoplasmic reticulum (ER) stress response. Here, we identify a previously unrecognized role for PIGBOS in cellular Ca2+ homeostasis. Manipulation of PIGBOS expression in HEK293T cells revealed that PIGBOS enhances Ca2+ signaling by promoting ER Ca2+ release through inositol 1,4,5-trisphosphate (IP3) receptors and subsequent mitochondrial Ca2+ uptake in response to histamine stimulation. In contrast, siRNA-mediated depletion or genetic ablation of PIGBOS markedly attenuated these responses. PIGBOS influenced Ca2+ transfer from the ER to mitochondria without affecting direct mitochondrial Ca2+ uptake and also promoted store-operated Ca2+ entry. Functional analyses demonstrated that the interaction of PIGBOS with the ER-resident chloride channel CLCC1 via its C-terminal region is required for this activity. Network analysis predicted a direct association between PIGBOS and CLCC1, as well as indirect connections with core Ca2+ signaling components, including IP3 receptors, STIM1, Orai1, and SERCA, whose expression was altered upon modulation of PIGBOS abundance. Loss of PIGBOS impaired mitochondrial respiration, reduced ATP production, and increased reactive oxygen species. Together, these findings establish PIGBOS as a key regulator of ER-mitochondrial Ca2+ signaling that couples Ca2+ dynamics to mitochondrial bioenergetics and cellular stress responses.
    Keywords:  CLCC1; Calcium signaling; Microprotein; PIGBOS
    DOI:  https://doi.org/10.1186/s12964-026-03027-3
  3. Aging (Albany NY). 2026 Jun 22. 18(1): 719-732
    The multifaceted inducers of cellular senescence.
    Hilah Gal, Valery Krizhanovsky.
      Cellular senescence is a stable form of cell-cycle arrest induced by diverse intrinsic and extrinsic stimuli. While senescence contributes to tumor suppression, wound repair, and placental and embryonic development, the chronic accumulation of senescent cells promotes tissue dysfunction, chronic inflammation, tumorigenesis, and age-related diseases. This review provides a comprehensive overview of the major inducers of cellular senescence, including DNA damage, oxidative and mitochondrial stress, telomere attrition, oncogene activation, cell-cell fusion, senescence-induced senescence and developmental stimuli, and summarizes the molecular mechanisms through which they trigger the senescence program. Although these stimuli differ widely, many converge to core effector pathways, resulting in a stable growth arrest. Understanding the varied stimuli and their underlying mechanisms of senescence induction is crucial for revealing the heterogeneity of senescent cells and developing interventions that modulate senescence during aging and disease.
    Keywords:  aging; cell senescence
    DOI:  https://doi.org/10.18632/aging.206391
  4. Trends Cancer. 2026 Jun 20. pii: S2405-8033(26)00126-3. [Epub ahead of print]
    Horizontal mitochondrial transfer and the tug-of-war between cancer cells and immune cells.
    Jaromir Novak, Denisa Hortova, Berwini Endaya, Magdalena Krulova, Michael V Berridge, Jiri Neuzil.
      Horizontal mitochondrial transfer (HMT) is an emerging field of cell biology. Since its discovery, HMT has been extensively studied in the context of cancer due to the essential role of mitochondria in fueling the proliferation of tumor cells. The role of HMT in cancer, however, reaches far beyond a simple mechanism of organelle acquisition. Indeed, several recent studies have demonstrated HMT from cancer to immune cells and vice versa, with a profound impact on antitumor immune responses and potentially on immunotherapy efficacy. In this opinion article, we propose that HMT should receive attention as another modulatable mechanism of the functional tug-of-war between cancer and immune cells, further contributing to the complexity of the tumor microenvironment and likely sculpting the outcome of competition between the two teams of cells.
    Keywords:  horizontal mitochondrial transfer; immunotherapy; tumor-infiltrating lymphocytes; tunneling nanotubes
    DOI:  https://doi.org/10.1016/j.trecan.2026.05.008
  5. Trends Immunol. 2026 Jun 25. pii: S1471-4906(26)00137-7. [Epub ahead of print]
    Mitochondrial Ca2+ signaling: A metabolic rheostat defining tumor and immune cell fate.
    Amélie E Bura, Andrea Rolong, Christophe Paget, Maxime Guéguinou.
      Mitochondrial calcium (mtCa2+) has long been framed as a bioenergetic regulator, yet evidence redefines it as a relevant immunometabolic switch. Within the tumor microenvironment, the mitochondrial calcium uniporter (MCU) complex and the NCLX-TMEM65 efflux axis maintain a 'Goldilocks zone' of Ca2+ homeostasis. This can be exploited by cancer cells to sustain oxidative phosphorylation and tricarboxylic acid-derived oncometabolite production, including succinate, fumarate, and 2-hydroxyglutarate, while imposing ionic and nutrient constraints on infiltrating immune cells. Chronic mtCa2+ overload in effector T cells drives mitochondrial dysfunction and exhaustion, while oxidative phosphorylation-dependent Ca2+ flux enforces the acquisition of an immunosuppressive profile in macrophages. Disrupting these tumor-immune ionic imbalances through selective MCU modulation or efflux pathway targeting offers a strategy to restore immune surveillance and/or enhance immune checkpoint inhibitor therapies.
    Keywords:  T cells; cancer; immune checkpoint blockade; immunometabolism; mitochondrial calcium signaling; tumor-associated macrophages
    DOI:  https://doi.org/10.1016/j.it.2026.05.012
  6. Cell Res. 2026 Jun 25.
    MitoCatch directs mitochondria delivery and prevents cell degeneration.
    Ana Paula Mendonça, Luca Scorrano.
      
    DOI:  https://doi.org/10.1038/s41422-026-01274-0
  7. J Cell Biol. 2026 Sep 07. pii: e202507087. [Epub ahead of print]225(9):
    PIKfyve influences inter-organelle contacts with lysosomes to modulate the endoplasmic reticulum.
    Nicala Jenkins, Zainab Adamji, Maria R Narciso, Nourhan R Almasri, Sharifa Lomiyev, Roberto J Botelho.
      Lysosomes clear unwanted cellular material delivered by constant membrane fusion. Membrane fission is thus required to balance lysosome size, number, and composition. PIKfyve is a lipid kinase that converts phosphatidylinositol-3-phosphate [PtdIns(3)P] to phosphatidylinositol-3,5-bisphosphate [PtdIns(3,5)P2] and promotes lysosome fission since lysosomes coalesce into larger, but fewer, organelles in its absence. Here, we reveal a role for PIKfyve in regulating ER dynamics. We show the ER is less reticulated and motile in cells inhibited for PIKfyve. Partly, this arises because lysosomes cluster perinuclearly and are less motile, which appears to arrest ER hitchhiking, a process in which lysosomes pull and form ER tubules. Secondly, the ER morphology is distorted because of hyper-tethering of protrudin, an ER transmembrane protein, to lysosomes via excess PtdIns(3)P and protrudin's FYVE domain. Our findings reveal that PIKfyve balances phosphoinositides at ER-lysosome contact sites to govern ER properties and have significant implications for our understanding of PIKfyve function and of diseases linked to its dysfunction.
    DOI:  https://doi.org/10.1083/jcb.202507087
  8. Nat Chem Biol. 2026 Jun 22.
    A ratiometric fluorescent reporter of mitochondrial sodium.
    Koushambi Mitra, Soyoung Kim, Daphne Oettinger, Sanjeev Uthishtran, Qian Zhao, Aneesh Tazhe Veetil, Joseph R Ramirez, Hening Lin, Senthil Arumugam, Yamuna Krishnan.
      Cells cope with salt stress, hypoxia or elevated cytosolic Ca2+ by regulating their mitochondrial Na+ levels. The discovery of the mitochondrial Na+/Ca2+ exchanger and its disease relevance has revealed the need to map mitochondrial Na+ in situ. Here we describe a ratiometric fluorescent reporter for Na+, denoted MitRatiNa, that reports mitochondrial Na+ levels independent of membrane potential and in diverse cell lines. Na+ in individual mitochondria varies greatly and, depending on cell type, can be as low as 1-5 mM or as high as 40 mM on average. We demonstrate that mitochondrial Na+ increases during cytosolic Ca2+ elevation, inhibition of glycolysis or respiration. Mitochondria in skin fibroblasts from healthy humans show a high Na+ population that disappears in fibroblasts of persons with mitochondrial diseases. The newfound ability to map absolute Na+ at the resolution of single mitochondria enables the dissection of regulatory mechanisms for mitochondrial Ca2+ and Na+ and potential identification of new therapeutic avenues.
    DOI:  https://doi.org/10.1038/s41589-026-02253-7
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