bims-mecosi 2024-08-18 papers

bims-mecosi

Biomed News

on Membrane contact sites

Issue of 2024–08–18
eleven papers selected by
Verena Kohler, Umeå University

Recent Advances on Synaptotagmin-Like Mitochondrial-Lipid Binding Protein Domain Containing Lipid Transfer Proteins.
Protocol for the isolation and purification of endoplasmic reticulum-plasma membrane junctions from the mouse brain.
Dynamic interaction of REEP5-MFN1/2 enables mitochondrial hitchhiking on tubular ER.
The tricalbin family of membrane contact site tethers is involved in the transcriptional responses of S. cerevisiae to glucose.
Quantitative assessment of morphological changes in lipid droplets and lipid-mito interactions with aging in brown adipose.
Unraveling the complex interplay between Mitochondria-Associated Membranes (MAMs) and cardiovascular Inflammation: Molecular mechanisms and therapeutic implications.
Hemal sinus basal laminae contact sites: a possible route between gonadal lumen and myoepithelial cells in the gonad of the sea star Patiria pectinifera.
Mitochondrial-derived compartments are multilamellar domains that encase membrane cargo and cytosol.
Sigma-1 receptor exerts protective effects on ameliorating nephrolithiasis by modulating endoplasmic reticulum-mitochondrion association and inhibiting endoplasmic reticulum stress-induced apoptosis in renal tubular epithelial cells.
Apoptosis mediated by crosstalk between mitochondria and endoplasmic reticulum: A possible cause of citrinin disruption of the intestinal barrier.
Glucocorticoid Deflazacort Normalizes the Ultrastructure of Skeletal Muscles and the State of the Colon Microbiota in Dystrophin-Deficient Mice.

Contact (Thousand Oaks). 2024 Jan-Dec;7:7 25152564241273646

Recent Advances on Synaptotagmin-Like Mitochondrial-Lipid Binding Protein Domain Containing Lipid Transfer Proteins.

Xuewen Hu, Yirui Cai, Wei-Ke Ji.

  The Synaptotagmin-like mitochondrial-lipid binding protein (SMP) domain is found in a group of ER-resident lipid transfer proteins that are recruited to membrane contact sites (MCSs) by adaptors. Deciphering the molecular basis underlying the recruitment of SMP proteins to specific MCS sheds light not only on their cellular localization but also on their biological functions at these sites. Here we summarize recent advances in SMP domain-containing lipid transfer proteins, focusing on a recent study showing the localization, regulation and cellular function of a specific SMP protein named testis expressed protein 2 (Tex2). TMEM55, a potential PIP phosphatase on late endosome/lysosomal (LE/lys) membranes, was identified as an adaptor that enables the recruitment of Tex2 to ER- LE/lys MCS. In addition, we have summarized several important questions about the regulation and physiological functions of Tex2 that remained unanswered.

Keywords:  ER-LE/lys MCSs; TMEM55B; Tex2

DOI:  https://doi.org/10.1177/25152564241273646
STAR Protoc. 2024 Aug 09. pii: S2666-1667(24)00418-0. [Epub ahead of print]5(3): 103253

Protocol for the isolation and purification of endoplasmic reticulum-plasma membrane junctions from the mouse brain.

Jason A Weesner, Diantha van de Vlekkert, Leigh Ellen Fremuth, Alessandra d'Azzo.

  Dynamic communication between intracellular organelles often takes place at specialized membrane contact sites that form between their membranes. Here we detail a procedure for the purification of endoplasmic reticulum-plasma membrane (ER-PM) junctions from the mouse brain. We describe steps for homogenizing isolated brain hemispheres and sequential centrifugation to remove the nuclear fraction from the other membrane fractions. We then detail procedures for separating the resulting crude membrane fractions by sucrose density gradients and purifying into their respective pellets. For complete details on the use and execution of this protocol, please refer to Weesner et al.1.

Keywords:  Cell Membrane; Cell separation/fractionation; Neuroscience

DOI:  https://doi.org/10.1016/j.xpro.2024.103253
J Cell Biol. 2024 Oct 07. pii: e202304031. [Epub ahead of print]223(10):

Dynamic interaction of REEP5-MFN1/2 enables mitochondrial hitchhiking on tubular ER.

Shue Chen, Yang Sun, Yuling Qin, Lan Yang, Zhenhua Hao, Zhihao Xu, Mikael Björklund, Wei Liu, Zhi Hong.

Mitochondrial functions can be regulated by membrane contact sites with the endoplasmic reticulum (ER). These mitochondria-ER contact sites (MERCs) are functionally heterogeneous and maintained by various tethers. Here, we found that REEP5, an ER tubule-shaping protein, interacts with Mitofusins 1/2 to mediate mitochondrial distribution throughout the cytosol by a new transport mechanism, mitochondrial "hitchhiking" with tubular ER on microtubules. REEP5 depletion led to reduced tethering and increased perinuclear localization of mitochondria. Conversely, increasing REEP5 expression facilitated mitochondrial distribution throughout the cytoplasm. Rapamycin-induced irreversible REEP5-MFN1/2 interaction led to mitochondrial hyperfusion, implying that the dynamic release of mitochondria from tethering is necessary for normal mitochondrial distribution and dynamics. Functionally, disruption of MFN2-REEP5 interaction dynamics by forced dimerization or silencing REEP5 modulated the production of mitochondrial reactive oxygen species (ROS). Overall, our results indicate that dynamic REEP5-MFN1/2 interaction mediates cytosolic distribution and connectivity of the mitochondrial network by "hitchhiking" and this process regulates mitochondrial ROS, which is vital for multiple physiological functions.

DOI: https://doi.org/10.1083/jcb.202304031
J Biol Chem. 2024 Aug 09. pii: S0021-9258(24)02166-5. [Epub ahead of print] 107665

The tricalbin family of membrane contact site tethers is involved in the transcriptional responses of S. cerevisiae to glucose.

Philipp Schlarmann, Keiko Sakuragi, Atsuko Ikeda, Yujia Yang, Saku Sasaki, Kazuki Hanaoka, Misako Araki, Tomoko Shibata, Muneyoshi Kanai, Kouichi Funato.

  Cellular organelles maintain areas of close apposition with other organelles at which the cytosolic gap in between them is reduced to a minimum. These membrane contact sites (MCS) are vital for organelle communication and are formed by molecular tethers that physically connect opposing membranes. Although many regulatory pathways are known to converge at MCS, a link between MCS and transcriptional regulation-the primary mechanism through which cells adapt their metabolism to environmental cues-remains largely elusive. In this study, we performed RNA-sequencing on Saccharomyces cerevisiae cells lacking tricalbin proteins (Tcb1, Tcb2, Tcb3), a family of tethering proteins that connect the endoplasmic reticulum with the plasma membrane and Golgi, to investigate if gene expression is altered when MCS are disrupted. Our results indicate that in the tcb1Δ2Δ3Δ strain, pathways responsive to a high-glucose environment, including glycolysis, fermentation, amino acid synthesis, and low-affinity glucose uptake, are upregulated. Conversely, pathways crucial during glucose depletion, such as the tricarboxylic acid (TCA) cycle, respiration, high-affinity glucose uptake, and amino acid uptake are downregulated. In addition, we demonstrate that the altered gene expression of tcb1Δ2Δ3Δ in glucose metabolism correlates with increased growth, glucose consumption, CO2 production, and ethanol generation. In conclusion, our findings reveal that tricalbin protein deletion induces a shift in gene expression patterns mimicking cellular responses to a high-glucose environment. This suggests that MCS play a role in sensing and signaling pathways that modulate gene transcription in response to glucose availability.

Keywords:  Membrane contact sites; amino acid; gene regulation; glucose metabolism; signaling; yeast

DOI:  https://doi.org/10.1016/j.jbc.2024.107665
J Cell Physiol. 2024 Aug 13.

Quantitative assessment of morphological changes in lipid droplets and lipid-mito interactions with aging in brown adipose.

Amber Crabtree, Kit Neikirk, Julia A Pinette, Aaron Whiteside, Bryanna Shao, Jessica Bedenbaugh, Zer Vue, Larry Vang, Han Le, Mert Demirci, Taseer Ahmad, Trinity Celeste Owens, Ashton Oliver, Faben Zeleke, Heather K Beasley, Edgar Garza Lopez, Estevão Scudese, Taylor Rodman, Kinuthia Kabugi, Alice Koh, Suzanne Navarro, Jacob Lam, Ben Kirk, Margaret Mungai, Mariya Sweetwyne, Ho-Jin Koh, Elma Zaganjor, Steven M Damo, Jennifer A Gaddy, Annet Kirabo, Sandra A Murray, Anthonya Cooper, Clintoria Williams, Melanie R McReynolds, Andrea G Marshall, Antentor Hinton.

  The physical characteristics of brown adipose tissue (BAT) are defined by the presence of multilocular lipid droplets (LDs) within the brown adipocytes and a high abundance of iron-containing mitochondria, which give it its characteristic color. Normal mitochondrial function is, in part, regulated by organelle-to-organelle contacts. For example, the contact sites that mediate mitochondria-LD interactions are thought to have various physiological roles, such as the synthesis and metabolism of lipids. Aging is associated with mitochondrial dysfunction, and previous studies show that there are changes in mitochondrial structure and the proteins that modulate organelle contact sites. However, how mitochondria-LD interactions change with aging has yet to be fully clarified. Therefore, we sought to define age-related changes in LD morphology and mitochondria-lipid interactions in BAT. We examined the three-dimensional morphology of mitochondria and LDs in young (3-month) and aged (2-year) murine BAT using serial block face-scanning electron microscopy and the Amira program for segmentation, analysis, and quantification. Our analyses showed reductions in LD volume, area, and perimeter in aged samples in comparison to young samples. Additionally, we observed changes in LD appearance and type in aged samples compared to young samples. Notably, we found differences in mitochondrial interactions with LDs, which could implicate that these contacts may be important for energetics in aging. Upon further investigation, we also found changes in mitochondrial and cristae structure for the mitochondria interacting with LDs. Overall, these data define the nature of LD morphology and organelle-organelle contacts during aging and provide insight into LD contact site changes that interconnect biogerontology with mitochondrial function, metabolism, and bioactivity in aged BAT.

Keywords:  brown adipose tissue (BAT); lipid droplets (LD); lipids; mitochondria; mito–lipid

DOI:  https://doi.org/10.1002/jcp.31340
Int Immunopharmacol. 2024 Aug 14. pii: S1567-5769(24)01451-6. [Epub ahead of print]141 112930

Unraveling the complex interplay between Mitochondria-Associated Membranes (MAMs) and cardiovascular Inflammation: Molecular mechanisms and therapeutic implications.

Xing Chen, Yang Yang, Zheng Zhou, Haihan Yu, Shuwei Zhang, Siyuan Huang, Ziqing Wei, Kaidi Ren, Yage Jin.

  Cardiovascular diseases (CVDs) represent a significant public health concern because of their associations with inflammation, oxidative stress, and abnormal remodeling of the heart and blood vessels. In this review, we discuss the intricate interplay between mitochondria-associated membranes (MAMs) and cardiovascular inflammation, highlighting their role in key cellular processes such as calcium homeostasis, lipid metabolism, oxidative stress management, and ERS. We explored how these functions impact the pathogenesis and progression of various CVDs, including myocardial ischemia-reperfusion injury, atherosclerosis, diabetic cardiomyopathy, cardiovascular aging, heart failure, and pulmonary hypertension. Additionally, we examined current therapeutic strategies targeting MAM-related pathways and proteins, emphasizing the potential of MAMs as therapeutic targets. Our review aims to provide new insights into the mechanisms of cardiovascular inflammation and propose novel therapeutic approaches to improve cardiovascular health outcomes.

Keywords:  Calcium homeostasis; Cardiovascular inflammation; Lipid metabolism; Mitochondria-associated membranes (MAMs); Therapeutic targets

DOI:  https://doi.org/10.1016/j.intimp.2024.112930
Protoplasma. 2024 Aug 14.

Hemal sinus basal laminae contact sites: a possible route between gonadal lumen and myoepithelial cells in the gonad of the sea star Patiria pectinifera.

Uliana E Shulga, Alexander V Kalachev.

  Sea stars are a group of marine invertebrates suitable for studying the hormonal regulation of reproduction and spawning. In spite of substantial progress in understanding how various substances such as 1-methyladenine act in their gonads, there are still many gaps concerning the fine details of their action. One such gap is how the gonadal wall contraction is induced. Recent literature data suggest that, upon 1-methyladenine stimulation, some cells within the gonadal lumen produce non-neuronal acetylcholine that, upon contact with the gonadal wall, induces contraction of myoepithelial cells. Our ultrastructural study of the gonads in the sea star Patiria pectinifera has shown, for the first time, that there are sites where the basal laminae bordering the hemal sinus directly contact one another and appear at this contact site as a single entity. These contact sites are often associated with hemidesmosome-like junctions that anchor male accessory cells or female follicle cells on one side of the site and myoepithelial cells on the opposite. We suggest that contraction-inducing substance is secreted from an accessory or follicle cell, passes through a basal lamina contact site, and on the opposite side of the contact site acts on a myoepithelial cell to induce its contraction.

Keywords:   Patiria pectinifera ; Acetylcholine; Gamete shedding; Sea stars

DOI:  https://doi.org/10.1007/s00709-024-01979-2
J Cell Biol. 2024 Nov 04. pii: e202307035. [Epub ahead of print]223(11):

Mitochondrial-derived compartments are multilamellar domains that encase membrane cargo and cytosol.

Zachary N Wilson, Matt West, Alyssa M English, Greg Odorizzi, Adam L Hughes.

Preserving the health of the mitochondrial network is critical to cell viability and longevity. To do so, mitochondria employ several membrane remodeling mechanisms, including the formation of mitochondrial-derived vesicles (MDVs) and compartments (MDCs) to selectively remove portions of the organelle. In contrast to well-characterized MDVs, the distinguishing features of MDC formation and composition remain unclear. Here, we used electron tomography to observe that MDCs form as large, multilamellar domains that generate concentric spherical compartments emerging from mitochondrial tubules at ER-mitochondria contact sites. Time-lapse fluorescence microscopy of MDC biogenesis revealed that mitochondrial membrane extensions repeatedly elongate, coalesce, and invaginate to form these compartments that encase multiple layers of membrane. As such, MDCs strongly sequester portions of the outer mitochondrial membrane, securing membrane cargo into a protected domain, while also enclosing cytosolic material within the MDC lumen. Collectively, our results provide a model for MDC formation and describe key features that distinguish MDCs from other previously identified mitochondrial structures and cargo-sorting domains.

DOI: https://doi.org/10.1083/jcb.202307035
Redox Rep. 2024 Dec;29(1): 2391139

Sigma-1 receptor exerts protective effects on ameliorating nephrolithiasis by modulating endoplasmic reticulum-mitochondrion association and inhibiting endoplasmic reticulum stress-induced apoptosis in renal tubular epithelial cells.

Hu Ke, Xiaozhe Su, Caitao Dong, Ziqi He, Qianlin Song, Chao Song, Jiawei Zhou, Wenbiao Liao, Chuan Wang, Sixing Yang, Yunhe Xiong.

  Oxalate-induced damage to renal tubular epithelial cells (RTECs) is an essential factor in the incident kidney stone, but the specific mechanism is unclear. Recent research has pinpointed interacting areas within the endoplasmic reticulum and mitochondria, called mitochondria-associated membranes (MAMs). These studies have linked endoplasmic reticulum stress (ERS) and oxidative imbalance to kidney disease development. The sigma-1 receptor (S1R), a specific protein found in MAMs, is involved in various physiological processes, but its role in oxalate-induced kidney stone formation remains unclear. In this study, we established cellular and rat models of oxalate-induced kidney stone formation to elucidate the S1R's effects against ERS and apoptosis and its mechanism in oxalate-induced RTEC injury. We found that oxalate downregulated S1R expression in RTECs and escalated oxidative stress and ERS, culminating in increased apoptosis. The S1R agonist dimemorfan up-regulated S1R expression and mitigated ERS and oxidative stress, thereby reducing apoptosis. This protective effect was mediated through S1R inhibition of the CHOP pathway. Animal experiments demonstrated that S1R's activation attenuated oxalate-induced kidney injury and alleviated kidney stone formation. This is the first study to establish the connection between S1R and kidney stones, suggesting S1R's protective role in inhibiting ERS-mediated apoptosis to ameliorate kidney stone formation.

Keywords:  Sigmar-1 receptor; apoptosis; dimemorfan; endoplasmic reticulum stress; kidney stone; mitochondria-associated endoplasmic reticulum membrane; oxalate; oxidative stress

DOI:  https://doi.org/10.1080/13510002.2024.2391139
Ecotoxicol Environ Saf. 2024 Aug 13. pii: S0147-6513(24)00953-9. [Epub ahead of print]284 116877

Apoptosis mediated by crosstalk between mitochondria and endoplasmic reticulum: A possible cause of citrinin disruption of the intestinal barrier.

Yuanyuan Li, Yongkang Wang, Zonghan Jiang, Chenglin Yang, You Wu, Aoao Wu, Qike Zhang, Xiaofang Liu, Bo Xiao, Yiya Feng, Jing Wu, Zengenni Liang, Zhihang Yuan.

  Citrinin (CTN) is a mycotoxin commonly found in contaminated foods and feed, posing health risks to both humans and animals. However, the mechanism by which CTN damages the intestine remains unclear. In this study, a model of intestinal injury was induced by administering 1.25 mg/kg and 5 mg/kg of CTN via gavage for 28 consecutive days in 6-week-old Kunming mice, aiming to explore the potential mechanisms underlying intestinal injury. The results demonstrate that CTN can cause structural damage to the mouse jejunum. Additionally, CTN reduces the protein expression of Claudin-1, Occludin, ZO-1, and MUC2, thereby disrupting the physical and chemical barriers of the intestine. Furthermore, exposure to CTN alters the structure of the intestinal microbiota in mice, thus compromising the intestinal microbial barrier. Meanwhile, the results showed that CTN exposure could induce excessive apoptosis in intestinal cells by altering the expression of proteins such as CHOP and GRP78 in the endoplasmic reticulum and Bax and Cyt c in mitochondria. The mitochondria and endoplasmic reticulum are connected through the mitochondria-associated endoplasmic reticulum membrane (MAM), which regulates the membrane. We found that the expression of bridging proteins Fis1 and BAP31 on the membrane was increased after CTN treatment, which would exacerbate the endoplasmic reticulum dysfunction, and could activate proteins such as Caspase-8 and Bid, thus further inducing apoptosis via the mitochondrial pathway. Taken together, these results suggest that CTN exposure can cause intestinal damage by disrupting the intestinal barrier and inducing excessive apoptosis in intestinal cells.

Keywords:  Apoptpsis; Citrinin; Intestinal; Intestinal barrier; Intestinal microbiota; MAM

DOI:  https://doi.org/10.1016/j.ecoenv.2024.116877
Bull Exp Biol Med. 2024 Aug 10.

Glucocorticoid Deflazacort Normalizes the Ultrastructure of Skeletal Muscles and the State of the Colon Microbiota in Dystrophin-Deficient Mice.

M V Dubinin, I B Mikheeva, A E Stepanova, E K Pavlova, T P Gazheeva, K N Belosludtsev.

  We studied the effect of enteral administration of the glucocorticoid deflazacort (DFC, 1.2 mg/kg per day, 28 days) on the state of skeletal muscles and tissue ultrastructure, as well as the composition of the colon microbiota in dystrophin-deficient mdx mice. DFC has been shown to reduce the intensity of degeneration/regeneration cycles in muscle fibers of mdx mice. This effect of DFC was accompanied by normalization of the size of sarcomeres of skeletal muscles of mdx mice, improvement of the ultrastructure of the subsarcolemmal population of mitochondria, and an increase in the number of organelles, as well as normalization of the number of contact interactions between the sarcoplasmic reticulum and mitochondria. In addition, DFC had a corrective effect on the colon microbiota of mdx mice, which manifested in an increase in the number of the Bifidobacterium genus microorganisms and a decrease in the level of E. coli with reduced enzymatic activity.

Keywords:  Duchenne muscular dystrophy; MAM contacts; deflazacort; microbiota; mitochondria

DOI:  https://doi.org/10.1007/s10517-024-06184-y