bims-lypmec 2026-05-17 papers

bims-lypmec

Biomed News

on Lysosomal positioning and metabolism in cardiomyocytes

Issue of 2026–05–17
ten papers selected by
Satoru Kobayashi, New York Institute of Technology

Mitochondria-lysosome contacts in aging: A mechanistic interface linking organelle homeostasis and cellular decline.
Lysosomal checkpoints in renal autoimmunity: from antigen processing to metabolic-immune crosstalk.
Distinct mitochondrial-derived vesicle pathways connect mitochondria with peroxisomes and lysosomes.
The miR-214-3p/CTSD Axis Regulates Lysosomal Homeostasis in Porcine Intestinal Epithelial Cells: A Preliminary Study.
Calcium Signaling Dysregulation in Diabetic Cardiomyopathy: Roles of STIM and Orai Channels.
A role for CASM in the repair of damaged Golgi architecture.
Nanosensor Quantifying Lysosomal Glycosidase Secretion from Single Living Cells.
Fatty Acids and Their Roles in Cardiac Physiology and Pathology: Mechanistic and Interventional Studies.
Tunnelling Nanotube-Mediated Lysosome Sharing Promotes Osteocyte Survival via Transcellular Autophagy.
Evaluation of cardiac histology and cell death markers during the progression of diabetes in a streptozotocin-induced diabetes rat model.

Mech Ageing Dev. 2026 May 08. pii: S0047-6374(26)00043-6. [Epub ahead of print]231 112191

Mitochondria-lysosome contacts in aging: A mechanistic interface linking organelle homeostasis and cellular decline.

YiFan Yan, Yuetong Li, Heng Ma.

  Mitochondria-lysosome contacts (MLCs) are emerging as a dynamic membrane interface that integrates organelle communication with cellular homeostasis. Rather than acting solely as intermediates of degradative trafficking, MLCs organize local calcium transfer, lipid exchange, Rab7-dependent contact remodeling, and mitochondrial quality control. These functions place MLCs at the intersection of mitochondrial fitness, lysosomal competence, metabolic adaptation, and stress signaling. Aging provides a particularly informative setting in which to examine this interface, because mitochondrial dysfunction and lysosomal decline co-emerge and reinforce one another during cellular aging. Current evidence suggests that aging does not simply increase or decrease MLCs, but instead remodels their dynamics, molecular composition, and functional output. Such remodeling may impair mitophagy, alter calcium and lipid coupling, amplify oxidative and inflammatory stress, and contribute to age-related disease phenotypes. In this review, we summarize the structural organization and regulatory logic of MLCs, examine their mechanistic roles in organelle homeostasis, and discuss how aging reshapes this interface in physiological and pathological contexts. We also highlight key methodological challenges and therapeutic opportunities for the field.

Keywords:  Aging; Lysosome; Membrane contact sites; Mitochondria-lysosome contacts; Mitochondrial quality control; Organelle homeostasis

DOI:  https://doi.org/10.1016/j.mad.2026.112191
Front Immunol. 2026 ;17 1830023

Lysosomal checkpoints in renal autoimmunity: from antigen processing to metabolic-immune crosstalk.

Zhengjing Fu, Xiang Xu.

  Lysosomes serve as critical intracellular hubs for degradation and signaling, playing a central role in maintaining immune homeostasis. In recent years, lysosomal functions have been conceptualized as a series of "checkpoints" that finely regulate the initiation and progression of autoimmune kidney diseases. This review systematically examines the multifaceted roles of lysosomal checkpoints in renal autoimmunity, with a focus on their mechanisms in autoantigen processing and presentation, immune cell activation and breakdown of tolerance, and the emerging area of metabolic-immune crosstalk. By integrating the latest research, this article aims to elucidate the potential of targeting lysosomal pathways as a novel therapeutic strategy for autoimmune kidney diseases such as lupus nephritis and ANCA-associated vasculitis.

Keywords:  antigen processing; immune tolerance; lupus nephritis; lysosomal checkpoint; metabolic reprogramming; renal autoimmunity

DOI:  https://doi.org/10.3389/fimmu.2026.1830023
Mitochondrion. 2026 May 12. pii: S1567-7249(26)00057-7. [Epub ahead of print]90 102167

Distinct mitochondrial-derived vesicle pathways connect mitochondria with peroxisomes and lysosomes.

Ayumu Sugiura, Kohta Nakamura, Heidi M McBride, Yasushi Okazaki.

  Mitochondrial-derived vesicles (MDVs) mediate selective trafficking of mitochondrial proteins and lipids to other organelles and contribute to organelle communication and mitochondrial quality control. While MDVs that deliver mitochondrial cargo to lysosomes have been extensively studied, the diversity of MDV pathways linking mitochondria to peroxisomes remains poorly understood. In particular, it is unclear how MDV pathways targeting peroxisomes relate to those delivering cargo to lysosomes, and whether cargos targeted to pre-existing peroxisomes utilize the same vesicular intermediates that participate in de novo peroxisome biogenesis. Here we examined MAPL trafficking using a peroxisome reconstitution system in PEX3-deficient fibroblasts. We found that MAPL is excluded from PEX3-positive pre-peroxisomal vesicles and instead is delivered to pre-existing peroxisomes, indicating that MAPL trafficking occurs through a pathway distinct from vesicles that initiate peroxisome formation. Structure-function analysis further revealed that a C-terminal amphipathic helix within MAPL is required for efficient targeting to peroxisomes. SNX9 depletion impaired both MAPL delivery to pre-existing peroxisomes and stress-induced lysosomal MDV pathways, whereas VPS35 depletion selectively reduced MAPL delivery without affecting lysosomal MDV pathways. In contrast, Parkin depletion impaired lysosomal MDV pathways but did not influence MAPL trafficking. Together, these findings demonstrate that mitochondria generate multiple classes of MDVs that are sorted into mechanistically distinct trafficking routes linking mitochondria with peroxisomes and lysosomes.

Keywords:  Lysosomes; Mitochondria; Mitochondrial-derived vesicles; Peroxisomes

DOI:  https://doi.org/10.1016/j.mito.2026.102167
Biology (Basel). 2026 Apr 28. pii: 693. [Epub ahead of print]15(9):

The miR-214-3p/CTSD Axis Regulates Lysosomal Homeostasis in Porcine Intestinal Epithelial Cells: A Preliminary Study.

Huixia Wang, Ruifeng Zhong, Wenli Li, Yijia Tao, Yali Li.

  Lysosomes are crucial for the function of fetal vacuolated enterocytes in neonatal piglets, yet how they are regulated by miRNAs remains poorly defined. Therefore, this study aimed to elucidate how miRNAs govern lysosomal homeostasis in the developing intestine. Using a neonatal piglet model of lysosomal dysfunction induced by imipramine (IMI), we identified ssc-miR-214-3p as a key down-regulated miRNA implicated in lysosomal pathways. In IPEC-J2 enterocytes, the miR-214-3p mimic ameliorated IMI cytotoxicity by restoring cell viability and migration while suppressing apoptosis. Further analysis revealed that miR-214-3p directly reversed the lysosomal defects triggered by IMI treatment. Specifically, it alleviated lysosomal alkalinization and markedly restored acid phosphatase (ACP) activity, indicating a recovery of the acidic hydrolytic environment. This restoration was also accompanied by the preservation of lysosomal membrane integrity and a consequent reduction in the nuclear translocation of transcription factor EB (TFEB). Furthermore, cathepsin D (CTSD) was validated as a direct target of miR-214-3p by luciferase assay, and its overexpression reversed the protective effects of the mimic on lysosomal acidification and lysosome-associated membrane protein 1 (LAMP1) levels. Collectively, our findings reveal a novel miR-214-3p/CTSD axis that regulates lysosomal homeostasis during neonatal intestinal maturation, providing a potential therapeutic target for porcine intestinal disorders.

Keywords:  CTSD; intestinal epithelial cells; lysosome; miR-214-3p; piglet

DOI:  https://doi.org/10.3390/biology15090693
Handb Exp Pharmacol. 2026 May 12.

Calcium Signaling Dysregulation in Diabetic Cardiomyopathy: Roles of STIM and Orai Channels.

Tarik Smani, Beltzane Dominguez-Liste, Marta de Jesús Gutiérrez-Barranco, Carlos Aspron-Martin, Celia Cordero-Sánchez, Eva M Calderón-Sánchez, Juan Antonio Rosado, Abdelkrim Hmadcha.

  Diabetes mellitus is a major metabolic disorder that significantly increases the risk of cardiovascular disease. Altered calcium (Ca2+) homeostasis, particularly through store-operated calcium entry (SOCE), has emerged as a critical pathway linking diabetes with cardiac dysfunction. Evidence indicates that SOCE is dysregulated in diabetes, but findings remain controversial. Some studies report reduced SOCE due to downregulation or impaired coupling of STIM1 and Orai1, leading to altered Ca2+ homeostasis and cardiac dysfunction. Others demonstrate enhanced SOCE linked to Orai and STIM isoforms upregulation, contributing to mitochondrial dysfunction, maladaptive hypertrophy, and metabolic remodeling in diabetic cardiomyopathy. Recent work also highlighted an unexpected role of STIM1 in fatty acid metabolism, linking Ca2+ signaling with energy substrate preference in the diabetic heart. This chapter synthesizes current evidence on the molecular mechanisms of STIM and Orai proteins in the regulation of SOCE under diabetic conditions, highlighting their roles in heart dysfunction.

Keywords:  Diabetic Cardiomyopathy; Fatty acid metabolism; Orai isoforms; STIM; Store-operated calcium entry

DOI:  https://doi.org/10.1007/164_2026_797
Autophagy. 2026 May 11.

A role for CASM in the repair of damaged Golgi architecture.

Seeun Oh, Saif Ullah, Bhaskar Saha, Michael A Mandell.

  The term CASM describes a process in which MAP1LC3B/LC3B and other Atg8-family proteins are covalently ligated to lipids in damaged endomembranes. While CASM is commonly described as a cytoprotective response to multiple types of membrane damage, how CASM helps cells maintain homeostasis is still unclear. Here, we show that CASM maintains Golgi apparatus architecture following the loss of TRIM46, a ubiquitin ligase with roles in microtubule organization. TRIM46 deficient cells were notable for enhanced TFEB-driven lysosomal biogenesis and Golgi ribbon fragmentation, with colocalization of the trans-Golgi marker TGOLN2 and the Atg8-family proteins LC3B and GABARAP. Further studies revealed that the Golgi Atg8ylation seen in TRIM46 knockout cells was not degradative and mechanistically resembled CASM. Genetic inhibition of CASM in TRIM46 deficient cells reduced TFEB activation and exacerbated the Golgi morphology defects, suggesting that CASM contributes to Golgi repair. Accordingly, Golgi reformation after drug-induced fragmentation was impaired upon knockdown of CASM genes. Together, these studies identify lysosomal biogenesis and CASM as coordinated features of a Golgi damage response, with CASM acting to preserve Golgi integrity.

Keywords:  Atg8ylation; CASM; TFEB; TRIM46; VAIL; autophagy; golgi damage/golgi fragmentation; lysosomal biogenesis; microtubule; tripartite motif

DOI:  https://doi.org/10.1080/15548627.2026.2673560
J Am Chem Soc. 2026 May 14.

Nanosensor Quantifying Lysosomal Glycosidase Secretion from Single Living Cells.

Yu-Ting Qi, Ru-Yan Zha, Xiao-Xiao Wang, Rui-Xue Gao, Ying Chen, Si-Yu Tian, Fu-Li Zhang, Xin-Wei Zhang, Wei-Hua Huang.

Secretory lysosomes serve as crucial regulatory effectors in immune cells, carrying out versatile functions related to both degradation and secretion. Disruption of their secretion processes can lead to immune imbalances, resulting in various health complications. However, current immunostaining-based methods hinder real-time and quantitative monitoring of lysosomal enzyme secretion while maintaining cell viability. Here, we developed a strategy combining artificial substrates and hybrid nanowire-nanopipette sensors to quantify the secretion of lysosomal glycosidases from single living macrophages. Glycosidase secretion was induced by frustrated phagocytosis of macrophages, and the glycosidases specifically recognized and hydrolyzed the corresponding artificial substrates ejected from the nanopipette to liberate electroactive aminophenol, which was subsequently detected by the nanowire electrode. This work provides, for the first time, an innovative and versatile methodology to monitor lysosomal enzyme secretion by quantitative assessment of glycosidase secreted from individual living macrophages, highlighting the dynamics of secretory lysosomes in maintaining immune homeostasis.

DOI: https://doi.org/10.1021/jacs.6c04507
Nutrients. 2026 Apr 30. pii: 1429. [Epub ahead of print]18(9):

Fatty Acids and Their Roles in Cardiac Physiology and Pathology: Mechanistic and Interventional Studies.

Rahul Mallick, Prasenjit Bhowmik, Premanjali Chowdhury, Asim K Duttaroy.

  Fatty acids serve dual roles in cardiac physiology: as energy substrates and as precursors of bioactive lipid mediators (prostaglandins, leukotrienes, oxylipins) from n-3/n-6 PUFAs that regulate inflammation, thrombosis, and remodeling. Saturated, monounsaturated, and trans fatty acids modulate metabolism and membrane function, thereby shaping these pathways. Clinically, n-3 long-chain PUFAs (EPA and DHA) reduce cardiovascular mortality and aid postischemic remodeling; however, high doses increase the risk of atrial fibrillation. By contrast, trans and saturated fatty acids promote dyslipidemia, dysfunction, and higher rates of coronary artery disease and heart failure. Mechanistically, fatty acid uptake via FABPpm, CD36 (FAT), and FATPs, along with β-oxidation and PPAR signaling, regulates metabolism, while COX/LOX/CYP pathways generate eicosanoids and resolvins that influence inflammation and repair. This review synthesizes evidence on the roles of fatty acids and oxylipins in lipotoxicity, heart failure, ischemia-reperfusion, and arrhythmias, and evaluates dietary and supplemental interventions to optimize cardiac lipid metabolism, aligning with fatty acid signaling.

Keywords:  cardiac metabolism; cardiac physiology; cardiovascular diseases; dietary interventions; fatty acids; lipotoxicity; n-3 fatty acids; trans fats

DOI:  https://doi.org/10.3390/nu18091429
Cell Prolif. 2026 May 14. e70226

Tunnelling Nanotube-Mediated Lysosome Sharing Promotes Osteocyte Survival via Transcellular Autophagy.

Jinbiao Qiang, Ronghao Jin, Tong Sha, Fang Zheng, Yijun Zhou, Yue Hu, Shuyu Zhang, Zhenming Yang, Mengdong Nie, Huanyu Luo, Xiaoduo Tang, Hao Guo, Zunxuan Xie, Jinwei Li, Hongchen Sun, Cangwei Liu, Ce Shi.

  Osteocytes, the central regulators of bone remodelling, are essential for maintaining bone homeostasis. Embedded in a nutrient-limited matrix and burdened by cumulative stress over their exceptionally long lifespan, how osteocytes sustain long-term viability remains elusive. Tunnelling nanotubes (TNTs) are newly described intercellular bridges that enable long-range transfer of organelles and have been implicated in stress adaptation. Here, we provide the first definitive identification of TNTs between cultured osteocytes, which exhibit canonical TNT morphology together with osteocyte-specific features. Functionally, osteocytic TNTs mediate intercellular transfer of membrane-bound cargo, predominantly lysosomes. Under nutrient deprivation, TNT formation and lysosome transfer are both increased, replenishing the lysosomal pool in stressed osteocytes. Transferred lysosomes then fuse with accumulated autophagosomes, thereby restoring impaired autophagic flux and suppressing apoptosis. This cytoprotective effect requires TNT integrity and intact autophagic flux. Although mitochondrial transfer is detectable, it does not confer comparable protection. The findings identify a transcellular autophagy pathway mediated by TNT-dependent lysosome sharing, revealing a previously unrecognized cooperative survival strategy among osteocytes. This work establishes a novel conceptual framework in osteocyte biology and suggests potential therapeutic avenues for bone diseases associated with osteocyte apoptosis and impaired bone remodelling.

Keywords:  apoptosis; intercellular communication; lysosomes; mitochondria; osteocytes; transcellular autophagy; tunnelling nanotubes

DOI:  https://doi.org/10.1111/cpr.70226
Animal Model Exp Med. 2026 May 14.

Evaluation of cardiac histology and cell death markers during the progression of diabetes in a streptozotocin-induced diabetes rat model.

Tamara Sáez, Ivo Carrasco-Wong, Juan Varas, Sebastián San Martín, Jaime A Riquelme, Rienzi Díaz-Navarro.

  The simultaneous characterization of histological alterations and distinct cell death pathways associated with diabetic cardiomyopathy (DCM) has not been comprehensively explored and may differ depending on the experimental model. We evaluated cardiac histological changes and markers of apoptosis, cell death associated with mitochondrial permeability transition pore (mPTP) opening (necrosis), and autophagy in early and advanced stages of streptozotocin (STZ)-induced diabetes in rats receiving insulin daily to prevent mortality while maintaining hyperglycemia. Adult male Sprague-Dawley rats (n = 4-5) were randomly assigned to receive STZ (diabetic group) or saline (mock) and followed up for 4 or 12 weeks. Hearts were processed for histological examination and immunohistochemical detection of active caspase-3, beclin-1, and cyclophilin D. STZ significantly increased glycemia at both time points, whereas body weight reduction was observed only at 12 weeks. No evidence of cardiac hypertrophy, fibrosis, or structural injury was detected in diabetic rats at either stage. Expression of caspase-3, beclin-1, and cyclophilin D decreased at 12 weeks compared with 4 weeks, regardless of treatment; however, cyclophilin D was elevated in diabetic hearts at 4 weeks. These results suggest an early susceptibility to mPTP opening under persistent hyperglycemia, despite the absence of overt histological damage. They also underscore the critical importance of insulin dosing and study duration when interpreting data from STZ-based models. Further studies are warranted to determine how even minimal insulin administration may shape the temporal dynamics of cell death during the progression of DCM.

Keywords:  cell death markers; diabetic cardiomyopathy; histology; insulin; streptozotocin‐induced diabetic rats

DOI:  https://doi.org/10.1002/ame2.70225