bims-mecosi 2026-09-27 papers

bims-mecosi

Biomed News

on Membrane contact sites

Issue of 2026–09–27
nine papers selected by
Verena Kohler, Umeå University

Dynamic imbalance of mitochondria-associated ER membranes in cardiovascular disease: mechanisms, context dependence and therapeutic potential.
Mitochondria-ER contact sites in neurological disorders.
Inter-Organelle Membrane Contact Sites as Physiological Regulatory Hubs in the Brain: From Neurons to Glial Cells.
Positive-Sense RNA Viruses Reprogramming Membrane Contact Sites to Remodel Organelles and Control Cell Fate.
Beyond parallel pathways: molecular integration and functional crosstalk between autophagy and endocytosis in plants.
Palmitic Acid Inhibits the Proliferation and Hypertrophy of Antler Chondrocytes by Disrupting Mitochondria-Associated Endoplasmic Reticulum Membrane Function.
Proteolytic remodeling by Yme1 enables mitochondrial-derived compartment formation.
Mitochondrial Ca2+ homeostasis in ovarian function and oocyte competence: from molecular transporters to early embryonic development.
Lipid droplet-mitochondria contact sites as druggable spatial-pharmacology targets in respiratory disease: cross-cell-type mechanisms and translational strategies.

Front Cell Dev Biol. 2026 ;14 1931748

Dynamic imbalance of mitochondria-associated ER membranes in cardiovascular disease: mechanisms, context dependence and therapeutic potential.

Yuhong Tang, Dezhao Liu, Beibei Luo, Feng Huang.

  Mitochondria-associated endoplasmic reticulum membranes (MAMs) are dynamic contact sites that coordinate structural and functional communication between the endoplasmic reticulum (ER) and mitochondria. By organizing tethering complexes, calcium channels, lipid-transfer machinery, and stress-responsive signaling modules, MAMs regulate Ca2+ homeostasis, lipid metabolism, mitochondrial dynamics, mitophagy, oxidative stress, endoplasmic reticulum stress, and cell fate determination. Increasing evidence indicates that MAMs dysfunction is critically involved in the initiation and progression of cardiovascular diseases (CVDs), including atherosclerosis, pulmonary hypertension, myocardial ischemia/reperfusion injury, myocardial infarction, diabetic cardiomyopathy, dilated cardiomyopathy, and heart failure. In these settings, disrupted or excessive ER-mitochondria coupling can trigger mitochondrial Ca2+ overload, metabolic remodeling, reactive oxygen species accumulation, inflammatory activation, and programmed cell death. Conversely, preserved or appropriately remodeled MAMs integrity supports mitochondrial bioenergetics, adaptive stress responses, and cardiomyocyte or vascular cell survival. This review summarizes the molecular architecture and biological functions of major MAMs-associated complexes, and discusses their context-dependent roles in cardiovascular pathophysiology. We further highlight the therapeutic potential of targeting MAMs structure and function as a strategy to restore organelle homeostasis and improve cardiovascular outcomes.

Keywords:  calcium homeostasis; cardiovascular disease; endoplasmic reticulum; mitochondria; mitochondria-associated membranes; mitochondrial dynamics

DOI:  https://doi.org/10.3389/fcell.2026.1931748
Anim Cells Syst (Seoul). 2026 ;30(1): 16-38

Mitochondria-ER contact sites in neurological disorders.

Eun Jin Jang, Jisoo Lee, Seungha Shin, Tran Diem Nghi, Sang Ki Park.

  Mitochondria-associated ER membranes (MAMs) are inter-organelle contact sites that mediate signaling between the ER and mitochondria. MAMs play crucial roles in Ca2+ transfer, lipid metabolism, mitochondrial respiration, protein homeostasis, autophagy, and ER stress. In the central nervous system (CNS), these functions are particularly important because neurons and glial cells require precise communication between ER and mitochondria to sustain various neuronal functions. Previous studies often interpreted the MAM dysfunction associated with disease as an alteration in ER-mitochondria coupling. More recently, however, MAMs are regarded as functionally specialized signaling platforms whose molecular composition is dynamic, cell type- and disease stage-dependent. Here, we discuss how MAM remodeling underlies a range of neurological diseases, including neurodegenerative and neurodevelopmental conditions, neuropsychiatric disorders, neuroinflammation, neuronal aging, and brain tumors.

Keywords:  MAM remodeling; MAMs; Mitochondria-associated ER membranes; neurological disorders; organelle homeostasis

DOI:  https://doi.org/10.1080/19768354.2026.2725542
Biomolecules. 2026 Aug 31. pii: 1257. [Epub ahead of print]16(9):

Inter-Organelle Membrane Contact Sites as Physiological Regulatory Hubs in the Brain: From Neurons to Glial Cells.

Yuchen Wu, Ginam Cho, Youngshin Lim.

  Inter-organelle membrane contact sites (MCSs) enable direct communication between organelles, and this communication is fundamental to cellular homeostasis, coordinated calcium (Ca2+) signaling, lipid metabolism, energy production, and stress responses. While MCSs are evolutionarily conserved, emerging evidence indicates that their organization and function are highly context dependent. In the brain, neurons and glial cells differ markedly in their physiological roles, morphologies, and metabolic demands, suggesting that inter-organelle contact networks might be specialized in a cell-type-dependent manner. Although much of the existing literature focuses on neurons, growing evidence indicates that these contact sites also play important roles in glial cells. Here, we review recent advances in our understanding of MCSs in the nervous system, focusing on cell-type-specific differences between neurons and glial cells. We highlight the spatial specialization of MCSs within neurons, emphasizing how subcellular localization shapes their functional output. Our analysis of the current literature suggests that neuronal MCSs are primarily optimized for rapid Ca2+ signaling and metabolic adaptation, whereas glial MCSs preferentially coordinate lipid metabolism, inflammatory signaling, and tissue homeostasis. We also review the context-dependent and disease-driven remodeling of MCSs in the brain, reflecting alterations in contact-site composition and function rather than simply increased or decreased organelle proximity. Furthermore, we discuss emerging therapeutic perspectives aimed at modulating inter-organelle communication in multiple neurological diseases and outline key unresolved questions and future directions necessary to elucidate how inter-organelle contact sites shape brain physiology and disease. Collectively, the evidence reviewed here indicates that MCSs serve as dynamic signaling platforms, with their specific physiological and pathological functions varying according to cell type, subcellular localization, and molecular composition.

Keywords:  brain homeostasis; glial cells; membrane contact sites; neurological diseases; neurons; organelle interactions; potential therapies

DOI:  https://doi.org/10.3390/biom16091257
Viruses. 2026 Sep 02. pii: 966. [Epub ahead of print]18(9):

Positive-Sense RNA Viruses Reprogramming Membrane Contact Sites to Remodel Organelles and Control Cell Fate.

Duo Zhang, Liqingyang Wang, Xiaokui Zhang, Fan Yang, Jihong Zhang, Wei Chen.

  Eukaryotic cells rely on a highly coordinated organelle network to maintain metabolism, signaling, stress adaptation and cell survival. Membrane contact sites (MCSs) provide essential platforms for inter-organelle communication. As obligate intracellular parasites, less attention has been given to how viral perturbation of MCSs may reshape the broader organelle communication network. In this review, we focus on positive-sense RNA viruses and virus-induced membrane contact sites (vMCSs), focusing on ER-associated tethering factors, lipid transfer pathways, calcium signaling modules, and replication organelle-host organelle interfaces. Also we discuss how viruses hijack conserved host tethering systems to connect viral replication compartments with lipid transfer machinery. Further, we explore how viruses establish vMCSs that couple replication compartments to host organelles, thereby coordinating cellular homeostasis. Together, these findings suggest that viral remodeling of MCSs should be understood not only as local manipulation of individual organelles but also as a network-level reorganization of cellular homeostasis.

Keywords:  cell fate control; membrane contact sites (MCSs); organelle-network cascades; positive-sense RNA viruses; replication organelles

DOI:  https://doi.org/10.3390/v18090966
Protoplasma. 2026 Sep 23.

Beyond parallel pathways: molecular integration and functional crosstalk between autophagy and endocytosis in plants.

Md Arif Sakil.

  Autophagy and endocytosis represent two fundamental membrane trafficking pathways that are essential for cellular homeostasis, stress responses, and development in plants. While traditionally studied as independent processes, mounting evidence reveals extensive crosstalk between these pathways at multiple levels, including shared molecular machinery, convergent trafficking routes, and coordinated regulation. This review examines the molecular mechanisms underlying the interplay between autophagy and endocytosis in plants, highlighting recent discoveries of shared protein complexes, membrane contact sites, and regulatory networks. Additionally, this review discusses how these pathways cooperate during stress responses, nutrient recycling, and protein quality control while also exploring their distinct roles in plant immunity and development. Understanding the intricate relationship between autophagy and endocytosis provides crucial insights into plant cell biology and offers potential strategies for improving stress tolerance and crop productivity.

Keywords:  Autophagy; Endocytosis; Endomembrane trafficking; Plant cell biology; Stress response; Vacuolar degradation

DOI:  https://doi.org/10.1007/s00709-026-02269-9
Antioxidants (Basel). 2026 Sep 02. pii: 1108. [Epub ahead of print]15(9):

Palmitic Acid Inhibits the Proliferation and Hypertrophy of Antler Chondrocytes by Disrupting Mitochondria-Associated Endoplasmic Reticulum Membrane Function.

Qiaoling Zhang, Zhanqing Yang, Xueyuan Yao, Yinfei Xing, Chenhao Wang, Baiyu Li, Zhanpeng Yue, Bin Guo.

  As the only mammalian appendage capable of complete regeneration, deer antlers serve as an invaluable model to investigate cartilage regrowth, but the underlying mechanism remains unclear. This study revealed that addition of palmitic acid (PA), an abundant long-chain saturated free fatty acid, inhibited the proliferation and hypertrophy of antler chondrocytes while promoting chondrocyte apoptosis. PA treatment activated NOTCH1 signaling and restrained the transport of Ca2+ from the cytosol to the endoplasmic reticulum (ER) via RBPJ (recombination signal-binding protein for immunoglobulin kappa J region)-targeted TMTC4 (transmembrane O-mannosyltransferase targeting cadherins 4), resulting in a reduction in ER Ca2+. Meanwhile, PA disrupted the structure and function of mitochondria-associated ER membranes (MAMs) via TGM2 (transglutaminase 2) through the cytosolic Ca2+-mediated PPP3CB (protein phosphatase 3 catalytic subunit beta)-NFATC2 (nuclear factor of activated T cells cytoplasmic 2) pathway. Further analysis demonstrated that PA induced mitochondrial dysfunction via MAM-mediated mitochondrial Ca2+ insufficiency, thereby restricting mitophagy and attenuating lysosomal acidification. This caused the leakage of mitochondrial reactive oxygen species (mtROS) from depolarized mitochondria into the cytosol via the mitochondrial permeability transition pore, thereby inducing lipid peroxidation, while the addition of ROS scavengers prevented the negative effects of chondrocyte proliferation and hypertrophy and protected chondrocytes from apoptosis in the context of PA. Collectively, PA treatment regulated the proliferation, apoptosis and hypertrophy of antler chondrocytes by disrupting MAM function.

Keywords:  MAM; NOTCH1 signaling; antler chondrocyte; mitochondrion; palmitic acid

DOI:  https://doi.org/10.3390/antiox15091108
bioRxiv. 2026 Apr 05. pii: 2026.04.03.716366. [Epub ahead of print]

Proteolytic remodeling by Yme1 enables mitochondrial-derived compartment formation.

Sai Sangeetha Balasubramaniam, Amy E Curtis, Jonathan R Friedman, Adam L Hughes.

Mitochondrial-derived compartments (MDCs) are remodeling domains that form from the outer mitochondrial membrane during metabolic and proteotoxic stress and selectively sequester hydrophobic membrane proteins. Although MDC formation depends on mitochondrial lipid composition and occurs at organelle contact sites, the molecular mechanisms that permit their biogenesis remain poorly defined. Here we identify the conserved inner mitochondrial membrane i-AAA protease Yme1 as a critical regulator of MDC formation. Loss of Yme1 blocks MDC biogenesis in response to multiple stressors, and this requirement depends on its proteolytic activity rather than secondary defects in mitochondrial morphology. Quantitative mitochondrial proteomics under MDC-inducing conditions revealed Yme1-dependent remodeling of lipid transfer proteins of the Ups family and components of the MICOS complex. Disruption of either pathway partially restores MDC formation in yme1Δ cells, while combined perturbation substantially bypasses the requirement for Yme1. Finally, Yme1 overexpression drives MDC formation in the absence of stress, although this activity remains constrained by metabolic conditions. Together, these findings support a model in which Yme1-dependent proteolysis relieves lipid- and MICOS-dependent constraints to permit MDC formation.

DOI: https://doi.org/10.64898/2026.04.03.716366
Front Cell Dev Biol. 2026 ;14 1963467

Mitochondrial Ca2+ homeostasis in ovarian function and oocyte competence: from molecular transporters to early embryonic development.

Xiaoqian Fu, Qianyi Huang, Huimei Wu, Lidan Liu.

  Mitochondrial Ca2+ homeostasis is a critical interface connecting ovarian cell signaling, energy metabolism, redox balance, and reproductive competence. Transient Ca2+ uptake into the mitochondrial matrix activates Ca2+-sensitive dehydrogenases, enhances reducing-equivalent generation, and supports oxidative phosphorylation. By contrast, sustained Ca2+ accumulation promotes reactive oxygen species production, membrane-potential collapse, mitochondrial permeability transition, and cell death. The identification of the mitochondrial calcium uniporter together with its regulators MICU1, MICU2, and EMRE, has established a molecular framework for mitochondrial Ca2+ influx. NCLX and its interacting protein TMEM65 contribute to Ca2+ efflux and determine recovery after individual Ca2+ transients. In ovarian cells and oocytes, endoplasmic reticulum (endoplasmic reticulum)-mitochondria contact sites, including the IP3R1-GRP75-VDAC1 axis, couple cytosolic Ca2+ signals to mitochondrial metabolism. Evidence from mouse, porcine, avian, zebrafish, Xenopus, and sea-urchin models implicates mitochondrial Ca2+ in follicular-cell survival, oocyte meiotic maturation, fertilization-associated Ca2+ oscillations, the oocyte-to-embryo transition, and early embryonic development. Obesity, aging, cryopreservation, heavy metals, environmental chemicals, and oxidative stress can disturb this system. However, mitochondrial Ca2+ dysregulation is not always readily separable from broader mitochondrial or ER dysfunction. Major limitations of the current literature include reliance on non-selective pharmacological agents, incomplete calibration of organelle-targeted indicators, insufficient temporal resolution, interspecies differences, and limited direct evidence from human oocytes. Future studies should integrate cell-type-specific genetic perturbation, quantitative multi-organelle Ca2+ imaging, mitochondrial bioenergetics, and long-term developmental assessment. Mitochondrial Ca2+ is a promising mechanistic node and candidate biomarker, but it is not yet a validated clinical target in reproductive medicine.

Keywords:  ER-mitochondria contact; MCU; MICU1; NCLX; embryo development; fertilization; mitochondrial Ca2+; oocyte competence

DOI:  https://doi.org/10.3389/fcell.2026.1963467
Front Cell Dev Biol. 2026 ;14 1935993

Lipid droplet-mitochondria contact sites as druggable spatial-pharmacology targets in respiratory disease: cross-cell-type mechanisms and translational strategies.

Shuting Li, Rongrong Bai.

  Lipid droplets and mitochondria form regulated contact sites whose molecular composition, phosphorylation state and spatial geometry now behave as measurable, druggable variables in living cells. The molecular toolkit has been mapped in liver, muscle and adipose tissue, yet its application to respiratory disease has lagged despite a lung-specific dependence on lipid biology that spans surfactant biogenesis, alveolar-macrophage lipid handling and fibroblast-driven remodelling. This review argues that the lipid-droplet-mitochondria contact site is an emerging spatial-pharmacology target in respiratory medicine, and organises the evidence into a three-way matrix with explicit grading of direct, indirect and cross-tissue evidence. A common molecular toolkit built around perilipin-family scaffolds, mitochondrial-outer-membrane tethers, an endoplasmic-reticulum bridging apparatus and the PFKL-PLIN2-CPT1A flux node (mechanistically established in hepatocellular carcinoma and inferred in lung) is rewired into cell-type-specific configurations across alveolar type 2 cells, macrophages, fibroblasts, endothelium and lung adenocarcinoma. That toolkit acquires a distinct disease role across idiopathic pulmonary fibrosis, chronic obstructive pulmonary disease, asthma, acute respiratory distress syndrome, tuberculosis, severe acute respiratory syndrome coronavirus two infection and lung cancer, generating a matrix of cell-type-by-disease configurations that no prior review has systematized. Four target axes, namely, tether occupancy, lipid flux, redox coupling and cell-type-precise delivery, converge geometrically at the interface and motivate combination strategies rather than pan-mitochondrial single-agent approaches. Inhaled lipid nanoparticles, mucus-penetrating carriers and engineered extracellular vesicles bring these targets within reach with cell-type precision. Endothelial contact-site biology is identified as the largest evidence gap and discussed candidly. The framework is offered as a roadmap for tether-axis compound development, contact-site engagement biomarkers and dual-axis inhaled therapeutics.

Keywords:  PFKL–PLIN2–CPT1A; PLIN5; chronic obstructive pulmonary disease; idiopathic pulmonary fibrosis; inhaled lipid nanoparticles; lipid droplet–mitochondria contact sites; lung adenocarcinoma; peridroplet mitochondria

DOI:  https://doi.org/10.3389/fcell.2026.1935993