bims-cesemi Biomed News
on Cellular senescence and mitochondria
Issue of 2026–04–12
seven papers selected by
Julio Cesar Cardenas, Universidad Mayor
  1. Organelle contact sites in cancer cells.
  2. Polyunsaturated lipids kill senescent cells by ferroptosis.
  3. Mitochondria-associated endoplasmic reticulum membranes as aging-sensitive signaling hubs in degenerative musculoskeletal diseases.
  4. Morphofunctional Heterogeneity and Plasticity of Glioblastoma Cells Induced to Senescence by Temozolomide.
  5. Endothelial cell senescence and mitochondrial dysfunction in vascular ageing.
  6. LIFe of the sugar-free party in cancer metabolism.
  7. Rethinking Mitochondria: The Extracellular Dimension.
  1. Cell Death Dis. 2026 Apr 04.
    Organelle contact sites in cancer cells.
    Ilaria Celotti, Matteo Scavezzon, Sabrina Toffanin, Alessia Ruzza, Federica Vianello, Elisabetta Zaltron, Carol Bastianello, Michela Rossini, Filippo Severin, Luigi Leanza.
      Membrane contact sites (MCSs) are defined as regions of functional proximity between membranes belonging to the same or different organelle types. These interactions are mediated by specialised proteins promoting the formation of these crosstalk hubs. Previously, organelles were considered to act independently in cellular physiology. However, it is now evident they carry out specific functions at MCSs. The first interactions described involved endoplasmic reticulum and mitochondria. Subsequently, many contacts involving different organelles emerged. MCSs affect several cellular processes, including intracellular signalling, lipid and ion homeostasis, transport of molecules, cellular metabolism, and redox balance. Disruption of these interactions has been described to be associated with various pathologies, including cancer. While the role of MCSs in tumours remains unclear, recent findings suggest they may influence cancer progression, so, in the near future, modulating organelle interactions could provide novel therapeutic options and develop new protocol to treat tumours.Schematic overview of intracellular MCSs, their effects on biological processes and the associated cancer-related outcomes. MCSs involve different cellular organelles allowing their intercommunication, finally participating in a plethora of cellular processes ranking from calcium and ions exchange, lipid transport and regulation of cell survival. Thus, MCSs modulation has been demonstrated to play a pivotal role in the modulation of cancer aggressiveness.
    DOI:  https://doi.org/10.1038/s41419-026-08674-5
  2. Cell Metab. 2026 Apr 07. pii: S1550-4131(26)00094-X. [Epub ahead of print]38(4): 643-644
    Polyunsaturated lipids kill senescent cells by ferroptosis.
    Mariantonietta D'Ambrosio, Jesús Gil.
      In a recent Cell Press Blue paper, Zhang et al. identify two polyunsaturated lipids that selectively eliminate senescent cells by inducing ferroptosis, uncovering this iron-dependent cell death pathway as a vulnerability for senescent cells. Their findings position ferroptosis induction as a promising strategy for targeting senescence and aging-associated diseases.
    DOI:  https://doi.org/10.1016/j.cmet.2026.02.021
  3. Ageing Res Rev. 2026 Apr 07. pii: S1568-1637(26)00123-6. [Epub ahead of print] 103131
    Mitochondria-associated endoplasmic reticulum membranes as aging-sensitive signaling hubs in degenerative musculoskeletal diseases.
    Linbo Peng, Kexin Wang, Limin Wu, Lei Yao, Bin Shen, Jian Li.
      Degenerative musculoskeletal diseases (DMDs), including osteoarthritis, osteoporosis, sarcopenia, and intervertebral disc degeneration, are highly prevalent age-related conditions characterized by progressive tissue dysfunction and loss of musculoskeletal integrity. Aging is accompanied by profound alterations in organelle homeostasis, metabolic signaling, and stress adaptation, among which mitochondria-endoplasmic reticulum communication has emerged as a critical regulatory axis. Mitochondria-associated membranes (MAMs) are specialized contact sites that spatially and functionally couple the endoplasmic reticulum and mitochondria, thereby coordinating calcium signaling, redox balance, lipid metabolism, and cell fate decisions. Accumulating evidence indicates that aging-related disruption of MAMs integrity and signaling contributes to mitochondrial dysfunction, oxidative stress, aberrant stress responses, and inflammatory activation across multiple musculoskeletal tissues. In this review, we synthesize current evidence linking MAMs-associated signaling pathways-including calcium flux, reactive oxygen species regulation, unfolded protein response signaling, autophagy, inflammasome activation, and regulated cell death-to the pathogenesis of major degenerative musculoskeletal diseases. We further highlight shared and tissue-specific mechanisms through which age-dependent MAMs dysregulation drives musculoskeletal degeneration. By framing MAMs as aging-sensitive signaling hubs, this review provides an integrated perspective on how organelle crosstalk contributes to degenerative musculoskeletal diseases and identifies conceptual frameworks for understanding disease convergence during musculoskeletal aging.
    Keywords:  Calcium homeostasis; Degenerative musculoskeletal diseases; ER–mitochondria crosstalk; Mitochondria-associated ER membranes; Mitochondrial dysfunction
    DOI:  https://doi.org/10.1016/j.arr.2026.103131
  4. Aging Cell. 2026 Apr;25(4): e70477
    Morphofunctional Heterogeneity and Plasticity of Glioblastoma Cells Induced to Senescence by Temozolomide.
    Solon Andrades da Rosa, Henrique Quaiato de Oliveira, Laura Boose de Mendonça, Nicole Borgmann de Oliveira, Mariane da Cunha Jaeger, Luiza Cherobini Pereira, Fernanda Dittrich Pinto Oliveira, Debora Santos-Sousa, Fernanda Saez-Calazans, Luana Lenz, Melike Lakadamyali, Guido Lenz, Eduardo Cremonese Filippi-Chiela.
      Several chemotherapeutics induce cancer cells to senescence, a persistent growth-arrest state associated with poor cancer prognosis. Relevant features in cancer cell biology, such as phenotypic plasticity and intercellular variability, are poorly understood for senescent cells (SnCs). This study examined the morphofunctional heterogeneity and dynamics of glioblastoma cells induced to senescence by Temozolomide (TMZ), focusing on pro-survival mechanisms, including autophagy and anti-apoptotic proteins, and phenotypic plasticity. TMZ triggered a proliferative arrest with canonical features of senescence. Two distinct morphotypes emerged with different kinetics: extension-rich (E-state) cells, which were predominant early on, and flattened (F-state) cells, which accumulated over time. These states were interchangeable, mostly from E-state to F-state, as revealed by single-cell tracking. F-state cells exhibited progressive enlargement of cellular and nuclear area, beyond extended survival, suggesting a more stable senescent phenotype despite lower p16 and autophagy levels than E-state cells. Late autophagy inhibition using hydroxychloroquine broadly sensitized both morphotypes, reducing enlarged cells. Otherwise, early autophagy inhibition with 3-methyladenine was not cytotoxic but led to E-state accumulation over F-state cells, suggesting an impact on morphometric dynamics. Beyond autophagy and p16, F-state cells also expressed lower levels of anti-apoptotic Bcl-2 proteins, indicating differential activation of survival pathways. Notably, the senolytics dasatinib preferentially eliminated E-state cells. These findings highlight the plasticity and heterogeneity of TMZ-induced senescent glioblastoma cells and emphasize the need for selective senotherapeutic strategies aiming to attenuate the pro-tumor effects exerted by SnCs on the tumor microenvironment.
    Keywords:  autophagy; cellular senescence; heterogeneity; phenotypic plasticity; senolytics
    DOI:  https://doi.org/10.1111/acel.70477
  5. Ageing Res Rev. 2026 Apr 02. pii: S1568-1637(26)00111-X. [Epub ahead of print]118 103119
    Endothelial cell senescence and mitochondrial dysfunction in vascular ageing.
    Iga Walczak, Maria Tarnawska, Klaudia Stawarska, Alicja Braczko, Aleksandra Paterek, Filip Rolski, Przemysław Leszek, Dorota Smolarek, Małgorzata Kapusta, Magdalena Narajczyk, Jean-Luc Cracowski, Beata Schlichtholz, Marcin Hellmann, Michał Mączewski, Barbara Kutryb-Zając.
      The vascular endothelium performs numerous regulatory functions that impact inflammatory responses, thrombosis, vascular tone and angiogenesis. Endothelial dysfunction is a key contributor to the pathogenesis of various human diseases, either as a primary trigger or as a consequence of organ damage. This review examines how ageing reshapes endothelial cell metabolism and mitochondrial function, progressively undermining endothelial homeostasis and resilience. Age-related endothelial alterations, including reduced nitric oxide bioavailability, heightened oxidative stress, impaired vasodilatory capacity and pro-inflammatory activation, arise from coordinated shifts in energy production, substrate utilization and redox signaling. In this context, cellular senescence, a stable arrest of the cell cycle accompanied by distinct metabolic, secretory and inflammatory changes, appears to be an important response to cumulative metabolic and mitochondrial stress. Senescent endothelial cells not only reflect this stress burden but also actively propagate dysfunction through sustained pro-inflammatory and pro-oxidant signalling, thereby accelerating vascular ageing. We highlight the central role of mitochondria in these events. Age-associated mitochondrial dysfunction disrupts bioenergetics, enhances reactive oxygen species generation and fuels chronic low-grade inflammation, amplifying endothelial decline. By bringing together current evidence-based knowledge on endothelial cell bioenergetics, mitochondrial impairment and metabolic reprogramming, this review identifies mitochondria-driven metabolic deterioration as a key mechanism underlying endothelial ageing and underscores mitochondrial metabolism as a promising, yet underexploited, therapeutic target in age-related vascular dysfunction.
    Keywords:  Bioenergetics; Endothelium; Metabolism; Mitochondria; Senescence; Vascular ageing
    DOI:  https://doi.org/10.1016/j.arr.2026.103119
  6. Trends Endocrinol Metab. 2026 Apr 09. pii: S1043-2760(26)00071-8. [Epub ahead of print]
    LIFe of the sugar-free party in cancer metabolism.
    Khaled Tighanimine, Brendan D Manning.
      Tumor cells can thrive in nutrient-scarce environments. Glucose deprivation can trigger adaptive responses that coordinate cell-cell communication within the tumor microenvironment (TME). Recently, Luciano-Mateo et al. demonstrated that glucose withdrawal promotes cancer cell secretion of the cytokine leukemia inhibitory factor (LIF), which exerts protumorigenic effects on the TME.
    Keywords:  LIF; N-glycosylation; PERK; glucose; lung cancer; metastasis
    DOI:  https://doi.org/10.1016/j.tem.2026.03.010
  7. Circ Res. 2026 Apr 10. 138(8): e326988
    Rethinking Mitochondria: The Extracellular Dimension.
    Laura Pena-Couso, Magdalena Makuch, Jose Angel Nicolas-Avila.
      Mitochondria are essential organelles that transform the energy contained in metabolic substrates into ATP while supporting numerous cellular processes. Traditionally regarded as strictly intracellular, growing evidence now demonstrates that mitochondria and mitochondria-derived components can also be released into the extracellular space, giving rise to extracellular mitochondria. extracellular mitochondria display remarkable heterogeneity, ranging from intact organelles to individual molecular components, free to vesicle-encapsulated structures, and with functional states spanning from severely damaged to metabolically active. Their release is mediated by tightly regulated mechanisms in both living and dying cells, and is influenced by cellular stress, activation state, and pathways that control mitochondrial selection, compartmentalization, trafficking, and extrusion. Extracellular release fulfills multiple functions across the organism, including quality control, modulation of cellular identity, inflammatory signaling, and functional support of recipient cells. In the cardiovascular system, extracellular mitochondria contribute to both homeostasis and disease progression. This review summarizes current knowledge of extracellular mitochondria forms, mechanisms of release, and pathophysiological relevance, and highlights their emerging potential as therapeutic targets in cardiovascular pathophysiology and beyond.
    Keywords:  cardiovascular system; extracellular space; homeostasis; mitochondria; organelles
    DOI:  https://doi.org/10.1161/CIRCRESAHA.125.326988
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