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Smooth endoplasmic reticulum

The tubular network with no ribosomes on it: lipid and steroid synthesis, calcium store, and where the hepatocyte keeps its drug-metabolising P450.

12 pictures and 25 papers. Its organelle page: Smooth endoplasmic reticulum.

Gallery

The left panel is the depositors' own "raw" file for this evaluation set and is already a thresholded membrane image, white on black, not greyscale electron microscopy. Two membrane forms are visible in it: long parallel lines, which are sheets cut edge-on, and small round profiles, which are tubules cut across. The tracing on the right marks the tubules and deliberately leaves the sheets unmarked, so the picture shows the distinction this page is built on rather than asserting it. Tubules occupy 13.0 percent of this 6 um crop of lean mouse liver.

Parlakgul G, Arruda AP, Pang S, Cagampan E, Min N, Guney E, Lee Y, Inouye K, Hess HF, Xu CS, Hotamisligil GS · CC0

High-magnification electron micrograph of a Leydig cell from an adult white crossbred boar (×18,600). A portion of the nucleus (N) is visible, along with abundant spherical mitochondria (M) and extensive, vesiculated smooth endoplasmic reticulum (black arrow), characteristic of steroidogenic cells. Lysosomes (L) and a Golgi apparatus (white arrow) are also visible.

Desaulniers, Ross, White et al 2026, Journal of Animal Science. Figure 5 · CC BY 4.0

Transmission electron microscopy Normal Leydig cells with no cytoplasmic vacuolation (M) are visible

Haldar, Gaikwad, Patra et al 2026, Cureus · CC BY 4.0

The classical secretory machinery and Golgi apparatus are predominantly localized to the perinuclear ER in neonatal and adult cardiac myocytes A, coimmunofluorescence labelling of neonatal rat ventricular myocytes with antibodies to the ER marker KDEL, the cis-Golgi marker GM130, the trans-Golgi marker TGN38 and the exosome marker CD63. B, coimmunofluorescence labelling of adult rat ventricular myocytes as described in (A). TOPRO, nuclei; scale bars = 20 um.

Sandmann, Brandenburg, Uhlenkamp et al 2026, The Journal of Physiology · CC BY 4.0

The ER architecture of DCM (MUT) iPSC-CMs is dysfunctional due to loss of membrane curvature. a – e Visualization of the ER membrane curvature in TPM1-L185F (MUT1) iPSC-CMs compared with isogenic control iPSC-CMs by cryo-electron microscopy. a Vitrified healthy control (WT1) iPSC-CM attached to the electron microscopy grid. Scale bar, 20 µm. b Cross-sectional lamella preparation using cryo-focused

Ignatyeva, Cheruiyot, Saleem et al 2026, Signal Transduction and Targeted Therapy · CC BY 4.0

REEP5 and MFN1/2 tethering facilitates mitochondrial hitchhiking on tubular ER. (A) Top: GI-SIM image of ER-mitochondria contacts in U2OS cell expressing REEP5 and MFN2 (also see Video 6). Bar: 2 um. (A'-A""") Time-lapse images of ER-mitochondria dynamic co-movements in four patterns: (A') middle part or (A") tip of mitochondria co-moved with tubular ER; (A'"") mitochondria comoved with tubular ER,

Chen, Sun, Qin et al 2024, The Journal of Cell Biology · CC BY 4.0

ER-shaping proteins undergo reverse distribution remodeling during early mitosis, with RTN4 enriched around centrosomes. (A) Representative images of ER protein (green) distributions in prometaphase HeLa cells. For tubular ER proteins (RTN4, RTN3, REEP5), ER sheet proteins (CLIMP63, KTN1, P180), and the ER marker Calnexin, cells were immunolabeled with the indicated antibodies. For pan-ER labeling

Xu, Liu, Wang et al 2026, Advanced Science · CC BY 4.0

LNPK marks ER junctions that enhance secretome mRNA translation. a, Representative image of LNPK-GFP and ER (Halo-Sec61b, cyan). Inset, enlarged view. Scale bar, 5 um. b, Top, translating SunTag(+) cytERM-SunTag-MS2 (grey) with overlapping SunTag (green) and LNPK (magenta). Bottom, non-translating SunTag(-) cytERM-SunTag-MS2, showing no colocalization with LNPK. Scale bars, 1 um.

Choi, Liao, Yoon et al 2025, Nature · CC BY 4.0

The ISGylation of CYP4Z1 facilitates its enzyme activity and subcellular localization in endoplasmic reticulum. a Quantitative results of MCF-7 or MDA-MB-231 cell lysates with or without ISG15 overexpression or knockdown for CYP4Z1 enzyme activity assay. b Quantitative results of HEK293T cell lysates with WT-CYP4Z1 or CYP4Z1 K259R/K279R/K502R overexpression for CYP4Z1 enzyme activity assay. c, d Colocalization of CYP4Z1 in MCF-7 cells with the endoplasmic reticulum (ER) probe (ER-Tracker Green), lysosome probe (LysoTracker Red DND-99), mitochondrial probe (MitoTracker Deep Red FM), or cytomembrane probe (CellLINK 505). e The colocalization coefficient between the control and the overexpressed ISG15 groups from parts c and d. f, g Colocalization of CYP4Z1 in MDA-MB-231 cells with the ER probe (ER-Tracker Green), lysosome probe (LysoTracker Red DND-99), mitochondrial probe (MitoTracker Deep Red FM), or cytomembrane probe (CellLINK 505). h The colocalization coefficient between the control and the overexpressed ISG15 groups from parts f and g.

Yuan, Lu, Han et al 2026, Experimental and Molecular Medicine · CC BY 4.0

A and B Transmission electron micrograph of the testis of DBP-(0 mg/kg) control or low doses DBP (1, 10 mg/kg) showing parts of seminiferous tubules and normal Leydig cells (LC) seen in the Interstitium. Seminiferous epithelium (SE), blood vessel (Bv), myofibroblast (Mc), boundary tissue (arrow heads). B High power view of part of a normal Leydig cell showing numerous mitochondria (Mt), abundant smooth endoplasmic reticulum (sER), a few lipid droplets (black arrows) and a mildly heterochromatic nucleus (Nc) Bar in Fig. 2A (5 um), Bar in Fig. 2B (10 um) (Japanese quail (Coturnix japonica, testicular Leydig cell); Figure 2B (normal Leydig cell, high power view).)

Bello, Madekurozwa, Groenewald et al 2023, Environmental Science and Pollution Research International · CC BY 4.0

Long narrow ER membranes in the control Phoenix cell line, panel A of a figure on ultrastructural aspects of ER stress in mutant Δ2-4VPS13B clones. Scale bar: 1 µm. ER, endoplasmic reticulum. (human (Phoenix cells, control condition); Figure 6, A (control).)

Morozova, Wolf, Kiseleva et al 2026, Cells · CC BY 4.0

Differential subcellular distribution of SERCA2a and SERCA2b in isolated rat MASMC. (A) Representative transmittance images (left) and corresponding fluorescence immunostainings (right) for SERCA2a (top) and SERCA2b (bottom) isoforms, visualized by confocal microscopy. Isolated rat MASMCs were immunostained with isoform-specific antibodies (SERCA2a or SERCA2b) and detected using Alexa Fluor 488-conjugated goat anti-rabbit IgG (green). Fluorescence intensity was subdivided into three distinct subcellular regions and quantified as described in Material and Methods. Nuclei were stained with DAPI (blue). Scale bar = 10 um. Adapted: IF panel A only; scatterplot panels B and C excluded. (rat (mesenteric artery smooth muscle cells); Figure 3, panel A only (confocal transmittance and IF for SERCA2a and SERCA2b; scatterplot panels B and C excluded; rows 10-640 of full figure, 799x630).)

Arriero-Carrillo, Lozano-Ruiz, Guerrero-Hernandez et al 2026, Frontiers in Physiology · CC BY 4.0

Papers

  1. Li T, Su T, Tang S, Cao K, Hua P, Gao J, et al. Necroptosis-related diseases are regulated by the unfolded protein response during endoplasmic reticulum stress. Genes Dis. 2027;14:102060. PMID: 42751065.
  2. Morozova KN, Wolf ER, Kiseleva EV, Smirnov AV, Pershina EG, Pristyazhnyuk IE. Modeling Cohen Syndrome in Phoenix Cells: VPS13B Loss Causes Organelle Stress, G1/S Delay, and Fibrillary Inclusion Bodies Formation. Cells. 2026;15:1535. PMID: 42738829.
  3. Danalache BA, Fallah A, Mercier F, Annabi B. The glucose-6-phosphatase system in cancer: from endoplasmic reticulum glucose-6-phosphate flux to stemness, immune escape, and therapeutic vulnerability. Front Oncol. 2026;16:1912198. PMID: 42539452.
  4. Niu Y, Han J, Song T, Tao X. Targeting endoplasmic reticulum stress: a novel therapeutic strategy for neuropathic pain. Front Pain Res (Lausanne). 2026;7:1761647. PMID: 42326878.
  5. Downes KW, Flood JR, Nans A, Van der Verren SE, Audhya A, Zanetti G. In situ cryo-ET defines the ultrastructure of ER exit sites in human cells. Nat Cell Biol. 2026;28:1258-1268. PMID: 42162283.
  6. Arriero-Carrillo CJ, Lozano-Ruiz H, Guerrero-Hernández A, Castro-Muñozledo F, Rueda A. Aldosterone increases the expression and subcellular localization of SERCA2a and SERCA2b in the rat mesenteric artery. Front Physiol. 2026;17:1811001. PMID: 42158499.
  7. Kwan X, Aslam MS, Liang H, Chen S. Gypenoside XLIX and Mitochondria-Associated ER Membranes in Non-Alcoholic Fatty Liver Disease: Mechanistic Insights and Emerging Perspectives. Molecules. 2026;31:1325. PMID: 42076006.
  8. Yan L, Xu Z, Yao Y, Awang T, Wang X, Wang Y, et al. The Erlin1/2 complex is a dynamic scaffold for membrane microdomain assembly on the endoplasmic reticulum. Mol Cell. 2026;86:1362-1376.e5. PMID: 41887216.
  9. Lu H, Feng X, Dai S, Zhu Y, Yuan K, Chen Y, et al. A novel MMP13 frameshift variant causes short stature via enhanced MMP13-HSPA5 interaction and activated endoplasmic reticulum stress. Clin Transl Med. 2026;16:e70648. PMID: 41877217.
  10. Qiao Y, Sun Y, Huang Y, Meng Q, Lin X, Wei W, et al. Roles of ER Membrane Protein Complex in Protein Biogenesis and Quality Control in the Lung and Beyond. Cell Prolif. 2026;59:e70191. PMID: 41804220.
  11. Kropp EM, Matono S, Wang OY, Robida AM, Kandarpa M, Grant JL, et al. Small molecule screening identifies cytotoxic endoplasmic reticulum-associated degradation inhibitors in multiple myeloma. Cell Death Dis. 2026;17:303. PMID: 41803084.
  12. Christer S, Marelja Z, Dibra I, Hauschild H, Berquez M, Gandhi H, et al. A Drosophila model for Dent's disease type 1 revealed impaired endoplasmic reticulum export of Cubilin as pathogenic mechanism. Kidney Int. 2026;109:957-970. PMID: 41690574.
  13. Chen B, Stark DC, Jadhav PV, Lynn-Nguyen TM, Halligan BS, Rossiter NJ, et al. BRD4-mediated ER membrane contact creates functionally distinct mitochondrial subtypes. Mol Cell. 2026;86:917-936.e12. PMID: 41690300.
  14. Soubeyrand S, Lau P, McPherson R. Differential regulation of ZFAS1 splice variants by endoplasmic reticulum stress in hepatocyte cell lines. FEBS Open Bio. 2026;16:1115-1131. PMID: 41649053.
  15. Araki T, Yokoyama K, Ida K, Inagaki Y, Kamiya A. Endoplasmic reticulum stress enhances unsaturated fatty acid-induced hepatocyte injury in human pluripotent stem cell-derived hepatic culture. BMC Gastroenterol. 2026;26:118. PMID: 41547733.
  16. Matsushima G, Yanase Y, Nakagawa T, Goda M, Ozawa K, Hosoi T. Endoplasmic reticulum stress and unfolded protein response in immune cell function. Front Immunol. 2025;16:1694102. PMID: 41208954.
  17. Karin M, Kim JY. Endoplasmic reticulum stress at the forefront of fatty liver diseases and cancer. Pharmacol Rev. 2025;77:100096. PMID: 41197470.
  18. Zhang Z, Cheng D, Dang J, Wang X, Fan H, Liu D. Decoding Endoplasmic Reticulum Stress on Chondrocyte Driving Osteoarthritis Development through Integrating Single-Cell and Transcriptomic Profiling. Int J Med Sci. 2025;22:3906-3923. PMID: 41049439.
  19. Stoyanov S, Barbolov M, Yaneva G, Tasinov O. Modulation of Endoplasmic Reticulum Stress by Selected Polyphenols from Sambucus ebulus L. Fruit. Plants (Basel). 2025;14:2748. PMID: 40941911.
  20. Obayashi K, Doi T, Sumida K, Endo M. Differential Induction of Endoplasmic Reticulum Stress Signaling by Antibody Isotypes: Implications for Plasma Cell Differentiation. Eur J Immunol. 2025;55:e202451428. PMID: 40285383.
  21. Li R, Sun K. Regulation of chondrocyte apoptosis in osteoarthritis by endoplasmic reticulum stress. Cell Stress Chaperones. 2024;29:750-763. PMID: 39515603.
  22. Zhang Z, Leng XK, Zhai YY, Zhang X, Sun ZW, Xiao JY, et al. Deficiency of ASGR1 promotes liver injury by increasing GP73-mediated hepatic endoplasmic reticulum stress. Nat Commun. 2024;15:1908. PMID: 38459023.
  23. Liu T, Li X, Pang M, Wang L, Li Y, Sun X. Machine learning-based endoplasmic reticulum-related diagnostic biomarker and immune microenvironment landscape for osteoarthritis. Aging (Albany NY). 2024;16:4563-4578. PMID: 38428406.
  24. Bello UM, Madekurozwa MC, Groenewald HB, Arukwe A, Aire TA. Changes in testicular histomorphometry and ultrastructure of Leydig cells in adult male Japanese quail exposed to di (n-butyl) phthalate (DBP) during the prepubertal period. Environ Sci Pollut Res Int. 2023;30:55402-55413. PMID: 36894732.
  25. Jin C, Felli E, Lange NF, Berzigotti A, Gracia-Sancho J, Dufour JF. Endoplasmic Reticulum and Mitochondria Contacts Correlate with the Presence and Severity of NASH in Humans. Int J Mol Sci. 2022;23:8348. PMID: 35955482.

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