bims-lypmec Biomed News
on Lysosomal positioning and metabolism in cardiomyocytes
Issue of 2026–01–04
six papers selected by
Satoru Kobayashi, New York Institute of Technology
  1. Repair of damaged lysosomes by TECPR1-mediated membrane tubulation during energy crisis.
  2. Unraveling Lysosomal Exocytosis: From Molecular Mechanisms to Physiological Functions.
  3. Editorial: The complex phenotype of diabetic cardiomyopathy: clinical indicators and novel treatment targets, volume II.
  4. TFEB coordinates autophagosome biogenesis and ribophagy during starvation via SQSTM1.
  5. Beyond the left ventricle: Right ventricular dysfunction as a critical determinant in type 1 diabetes-related cardiomyopathy.
  6. ENT3: A lysosomal urate transporter regulating urate disposition and macrophage inflammation.
  1. Cell Res. 2026 Jan 02.
    Repair of damaged lysosomes by TECPR1-mediated membrane tubulation during energy crisis.
    Hanmo Chen, Chaojun Zhang, Yuhui Fu, Linsen Li, Xiaoyu Qiao, Shen Zhang, Hanyan Luo, She Chen, Xiaoxia Liu, Qing Zhong.
      Lysosomes are essential for cellular homeostasis, serving as degradative organelles that recycle nutrients. Whether and how lysosomes maintain membrane integrity under energy stress is poorly understood. Here, we found that the uptake of lipid droplets by lysosomes during glucose starvation provokes disruption of lysosomal membranes. We identified tectonin beta-propeller repeat-containing protein 1 (TECPR1) as a critical mediator of lysosomal repair during glucose starvation or LLOMe-induced lysosomal membrane permeabilization. TECPR1 is recruited to damaged lysosomes via interaction with PI4P on damaged lysosomal membranes. It interacts with KIF1A to facilitate tubule formation from damaged lysosomes, enabling the removal of damaged membrane components and promoting lysosomal repair. Our in vitro reconstituted tubulation process provided further evidence that TECPR1 coordinates with KIF1A to drive tubulation from PI4P-enriched giant unilamellar vesicles. TECPR1-mediated lysosomal repair is essential for maintaining lipid metabolism and cellular survival during an energy crisis, as TECPR1 deficiency exacerbates starvation-induced liver damage in a high-fat diet-induced MAFLD mouse model. Our findings demonstrate a previously unrecognized role of TECPR1 in lysosomal repair, revealing its critical contributions to energy stress adaptation and liver protection. This work provides new insight into mechanisms of lysosomal repair and their implications for metabolic and lysosome-related disorders.
    DOI:  https://doi.org/10.1038/s41422-025-01193-6
  2. Traffic. 2026 Mar;27(1): e70026
    Unraveling Lysosomal Exocytosis: From Molecular Mechanisms to Physiological Functions.
    Shanshan Jiang, Jingyi Fu, Shan Li, Zehui Li, Qirui Zhao, Yuqi Yin, Mei Yang, Yonghua Wang.
      Lysosomal exocytosis is a fundamental cellular process that involves the fusion of lysosomes with the plasma membrane and the release of lysosomal contents into the extracellular space. This review provides an in-depth analysis of the molecular mechanisms, physiological functions, and disease implications of lysosomal exocytosis, highlighting recent advances and novel aspects. We discuss the intricate molecular machinery that orchestrates lysosomal trafficking, docking, and fusion, as well as the critical roles of lysosomal exocytosis in maintaining cellular homeostasis, facilitating intercellular communication, and contributing to specialized cellular functions. Additionally, the review explores the complex involvement of lysosomal exocytosis in various disease states, including lysosomal storage disorders, neurodegenerative diseases, cancers, and immune system disorders, underlining its potential as a therapeutic target. By identifying current knowledge gaps and providing future research directions, this review aims to stimulate further investigation into the multifaceted nature of lysosomal exocytosis and its implications for human health and disease.
    DOI:  https://doi.org/10.1111/tra.70026
  3. Front Endocrinol (Lausanne). 2025 ;16 1752170
    Editorial: The complex phenotype of diabetic cardiomyopathy: clinical indicators and novel treatment targets, volume II.
    Priyanka Choudhury, Yin Cai.
      
    Keywords:  angiogenesis; biomarker; diabetic cardiomyopathy; lipid metabolism; multimodality imaging
    DOI:  https://doi.org/10.3389/fendo.2025.1752170
  4. Sci Adv. 2026 Jan 02. 12(1): eaea9302
    TFEB coordinates autophagosome biogenesis and ribophagy during starvation via SQSTM1.
    Maria Iavazzo, Laura Cinque, Sophie Levantovsky, Castrese Morrone, Jlenia Monfregola, Andrea Raimondi, Elena Polishchuk, Rossella De Cegli, Diego Carrella, Edoardo Nusco, Luigi Ferrante, Francesca Sacco, Lisa B Frankel, Christian Behrends, Carmine Settembre.
      (Macro)autophagy is a conserved cellular degradation pathway that delivers substrates to lysosomes via autophagosomes. Among various physiological stimuli, nutrient starvation is the most potent inducer of autophagy. In response to starvation, transcription factor EB (TFEB) is activated and up-regulates a broad set of autophagy-related genes. However, the mechanisms by which TFEB promotes autophagosome biogenesis remain incompletely understood. Here, we demonstrate that TFEB-mediated transcriptional induction of sequestosome 1 (SQSTM1; p62) triggers the formation of SQSTM1-positive bodies that recruit essential autophagy factors, thereby initiating autophagosome biogenesis. Genetic disruption of TFEB-dependent SQSTM1 regulation markedly impairs starvation-induced autophagy, underscoring the critical role of the TFEB-SQSTM1 axis in the autophagic response to nutrient stress. Furthermore, we show that these SQSTM1 bodies contain ubiquitinated ribosomal proteins and that TFEB promotes ribosomal protein ubiquitination by inducing the E3 ubiquitin ligase ZNF598. Collectively, our findings uncover a transcriptionally coordinated mechanism that regulates both autophagosome biogenesis and substrate ubiquitination, facilitating efficient cargo clearance during starvation-induced autophagy.
    DOI:  https://doi.org/10.1126/sciadv.aea9302
  5. World J Diabetes. 2025 Dec 15. 16(12): 114485
    Beyond the left ventricle: Right ventricular dysfunction as a critical determinant in type 1 diabetes-related cardiomyopathy.
    Tong-Jian Zhao, Nian-Zhe Sun.
      Diabetic cardiomyopathy (DCM) has long been considered as a left ventricular (LV) disease with diastolic dysfunction preceding systolic dysfunction in diabetes. However, it is increasingly recognized that the right ventricle (RV) is also affected by diabetes and may be independently responsible for adverse outcomes in diabetic patients with or without LV failure. Yu et al conducted a 30-week longitudinal evaluation of biventricular function and pathology in OVE26 diabetic mice and revealed early diastolic dysfunction preceding systolic decline, suggesting that early LV diastolic impairment precedes the later onset of systolic dysfunction. With age, the animals developed fibrosis, hypertrophy, and pulmonary arterial hypertension in the RV. The purpose of this editorial is to contextualize these findings within the existing literature by highlighting the interplay between cardiac chambers and the vasculature. We also seek to reiterate that DCM is a condition extending beyond left ventricular dysfunction. As the authors note, the right side of the heart may remain "the forgotten ventricle" in diabetic patients. We hope that the mechanisms discussed in this paper will help researchers to understand the pathogenesis of cardiovascular disease in this context and encourage clinicians to be more attentive to the associated clinical symptoms.
    Keywords:  Cardiac remodeling; Diabetic cardiomyopathy; Fibrosis; Left ventricular dysfunction; Pulmonary arterial hypertension; Right ventricular dysfunction; Type 1 diabetes
    DOI:  https://doi.org/10.4239/wjd.v16.i12.114485
  6. iScience. 2025 Dec 19. 28(12): 114249
    ENT3: A lysosomal urate transporter regulating urate disposition and macrophage inflammation.
    Isamu Matake, Tomoya Yasujima, Hirotaka Matsuo, Akiyoshi Nakayama, Yu Toyoda, Tappei Takada, Katsuhisa Inoue, Takahiro Yamashiro, Hiroaki Yuasa.
      Urate is the final oxidation product of purine metabolism in humans, and its extracellular accumulation leads to the formation of monosodium urate (MSU) crystals that trigger gout. Although several plasma membrane transporters involved in urate reabsorption and excretion have been identified, the mechanisms governing intracellular urate clearance remain unclear. Here, we show that equilibrative nucleoside transporter 3 (ENT3/SLC29A3) functions as a proton-coupled urate exporter from lysosomes. Using a recombinant ENT3 that localizes to the plasma membrane, we determined its urate transport kinetics (K m ≈ 1.15 mM), establishing ENT3 as a low-affinity, high-capacity urate transporter. In differentiated THP-1 macrophage-like cells, ENT3 knockdown impaired clearance of phagocytosed MSU, while reducing interleukin-1β secretion likely due to diminished adenosine-mediated inflammatory signaling. These findings reveal an unrecognized role of ENT3 in lysosomal urate handling and inflammation, suggesting that ENT3 dysfunction may contribute to gout and other urate-associated disorders.
    Keywords:  Biochemistry; Cell biology; Immunology
    DOI:  https://doi.org/10.1016/j.isci.2025.114249
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