bims-mecosi Biomed News
on Membrane contact sites
Issue of 2024–05–05
seven papers selected by
Verena Kohler, Umeå University
  1. The tether function of the anoctamins.
  2. Progress of mitochondrial and endoplasmic reticulum-associated signaling and its regulation of chronic liver disease by Chinese medicine.
  3. Hansenula polymorpha cells lacking the ER-localized peroxins Pex23 or Pex29 show defects in mitochondrial function and morphology.
  4. Mitochondria-associated endoplasmic reticulum membranes as a therapeutic target for cardiovascular diseases.
  5. N, N-Dimethyltryptamine, a natural hallucinogen, ameliorates Alzheimer's disease by restoring neuronal Sigma-1 receptor-mediated endoplasmic reticulum-mitochondria crosstalk.
  6. The VAMP-associated protein VAP27-1 plays a crucial role in plant resistance to ER stress by modulating ER-PM contact architecture in Arabidopsis.
  7. Ceramide sorting into non-vesicular transport is independent of acyl chain length in budding yeast.
  1. Cell Calcium. 2024 Apr 20. pii: S0143-4160(24)00033-2. [Epub ahead of print]121 102875
    The tether function of the anoctamins.
    Wei-Yin Lin, Woo Young Chung, Shmuel Muallem.
      The core functions of the anoctamins are Cl- channel activity and phosphatidylserine (and perhaps other lipids) scrambling. These functions have been extensively studied in various tissues and cells. However, another function of the anoctamins that is less recognized and minimally explored is as tethers at membrane contact sites. This short review aims to examine evidence supporting the localization of the anoctamins at membrane contact sites, their tether properties, and their functions as tethers.
    Keywords:  Anoctamins; Tethers
    DOI:  https://doi.org/10.1016/j.ceca.2024.102875
  2. World J Hepatol. 2024 Apr 27. 16(4): 494-505
    Progress of mitochondrial and endoplasmic reticulum-associated signaling and its regulation of chronic liver disease by Chinese medicine.
    Yang Zheng, Yi-Hui Zheng, Jia-Hui Wang, Tie-Jian Zhao, Lei Wang, Tian-Jian Liang.
      The endoplasmic reticulum (ER) is connected to mitochondria through mitochondria-associated ER membranes (MAMs). MAMs provide a framework for crosstalk between the ER and mitochondria, playing a crucial role in regulating cellular calcium balance, lipid metabolism, and cell death. Dysregulation of MAMs is involved in the development of chronic liver disease (CLD). In CLD, changes in MAMs structure and function occur due to factors such as cellular stress, inflammation, and oxidative stress, leading to abnormal interactions between mitochondria and the ER, resulting in liver cell injury, fibrosis, and impaired liver function. Traditional Chinese medicine has shown some research progress in regulating MAMs signaling and treating CLD. This paper reviews the literature on the association between mitochondria and the ER, as well as the intervention of traditional Chinese medicine in regulating CLD.
    Keywords:  Chronic liver disease; Endoplasmic reticulum; Mitochondria; Mitochondria-associated ER membranes; Traditional Chinese medicine
    DOI:  https://doi.org/10.4254/wjh.v16.i4.494
  3. Biol Open. 2024 Apr 29. pii: bio.060271. [Epub ahead of print]
    Hansenula polymorpha cells lacking the ER-localized peroxins Pex23 or Pex29 show defects in mitochondrial function and morphology.
    Haiqiong Chen, Rinse de Boer, Arjen M Krikken, Fei Wu, Ida van der Klei.
      Pex23 family proteins localize to the endoplasmic reticulum and play a role in peroxisome and lipid body formation. The yeast Hansenula polymorpha contains four members: Pex23, Pex24, Pex29 and Pex32. We previously showed that loss of Pex24 or Pex32 results in severe peroxisomal defects, caused by reduced peroxisome-endoplasmic reticulum contact sites. We now analyzed the effect of the absence of all four Pex23 family proteins on other cell organelles. Vacuoles were normal in all four deletion strains. The number of lipid droplets was reduced in pex23 and pex29, but not in pex24 and pex32 cells, indicating that peroxisome and lipid droplet formation require different Pex23 family proteins in H. polymorpha. In pex23 and pex29 cells mitochondria were fragmented and clustered accompanied by reduced levels of the fusion protein Fzo1. Deletion of DNM1 suppressed the morphological phenotype of pex23 and pex29 cells, suggesting that mitochondrial fusion is affected. pex23 and pex29 cells showed retarded growth and reduced mitochondrial activities. The growth defect was partially suppressed by DNM1 deletion as well as by an artificial mitochondrion-endoplasmic reticulum tether. Hence, the absence of Pex23 family proteins may influence mitochondrion-endoplasmic reticulum contact sites.
    Keywords:  Lipid droplets; Mitochondria; Pex23 family; Yeast
    DOI:  https://doi.org/10.1242/bio.060271
  4. Front Pharmacol. 2024 ;15 1398381
    Mitochondria-associated endoplasmic reticulum membranes as a therapeutic target for cardiovascular diseases.
    Yanqiu Ding, Nanyang Liu, Dawu Zhang, Lijun Guo, Qinghua Shang, Yicheng Liu, Gaocan Ren, Xiaochang Ma.
      Cardiovascular diseases (CVDs) are currently the leading cause of death worldwide. In 2022, the CVDs contributed to 19.8 million deaths globally, accounting for one-third of all global deaths. With an aging population and changing lifestyles, CVDs pose a major threat to human health. Mitochondria-associated endoplasmic reticulum membranes (MAMs) are communication platforms between cellular organelles and regulate cellular physiological functions, including apoptosis, autophagy, and programmed necrosis. Further research has shown that MAMs play a critical role in the pathogenesis of CVDs, including myocardial ischemia and reperfusion injury, heart failure, pulmonary hypertension, and coronary atherosclerosis. This suggests that MAMs could be an important therapeutic target for managing CVDs. The goal of this study is to summarize the protein complex of MAMs, discuss its role in the pathological mechanisms of CVDs in terms of its functions such as Ca2+ transport, apoptotic signaling, and lipid metabolism, and suggest the possibility of MAMs as a potential therapeutic approach.
    Keywords:  cardiovascular diseases; coronary atherosclerosis; mitochondria-associated endoplasmic reticulum membrane; myocardial ischemia; therapeutic target
    DOI:  https://doi.org/10.3389/fphar.2024.1398381
  5. Alzheimers Res Ther. 2024 May 01. 16(1): 95
    N, N-Dimethyltryptamine, a natural hallucinogen, ameliorates Alzheimer's disease by restoring neuronal Sigma-1 receptor-mediated endoplasmic reticulum-mitochondria crosstalk.
    Dan Cheng, Zhuo-Gui Lei, Kin Chu, Oi Jin Honey Lam, Chun Yuan Chiang, Zhang-Jin Zhang.
       BACKGROUND: Aberrant neuronal Sigma-1 receptor (Sig-1r)-mediated endoplasmic reticulum (ER)- mitochondria signaling plays a key role in the neuronal cytopathology of Alzheimer's disease (AD). The natural psychedelic N, N-dimethyltryptamine (DMT) is a Sig-1r agonist that may have the anti-AD potential through protecting neuronal ER-mitochondrial interplay.
    METHODS: 3×TG-AD transgenic mice were administered with chronic DMT (2 mg/kg) for 3 weeks and then performed water maze test. The Aβ accumulation in the mice brain were determined. The Sig-1r level upon DMT treatment was tested. The effect of DMT on the ER-mitochondrial contacts site and multiple mitochondria-associated membrane (MAM)-associated proteins were examined. The effect of DMT on calcium transport between ER and mitochondria and the mitochondrial function were also evaluated.
    RESULTS: chronic DMT (2 mg/kg) markedly alleviated cognitive impairment of 3×TG-AD mice. In parallel, it largely diminished Aβ accumulation in the hippocampus and prefrontal cortex. DMT restored the decreased Sig-1r levels of 3×TG-AD transgenic mice. The hallucinogen reinstated the expression of multiple MAM-associated proteins in the brain of 3×TG-AD mice. DMT also prevented physical contact and calcium dynamic between the two organelles in in vitro and in vivo pathological circumstances. DMT modulated oxidative phosphorylation (OXPHOS) and ATP synthase in the in vitro model of AD.
    CONCLUSION: The anti-AD effects of DMT are associated with its protection of neuronal ER-mitochondria crosstalk via the activation of Sig-1r. DMT has the potential to serve as a novel preventive and therapeutic agent against AD.
    Keywords:  Alzheimer’s disease; ER-mitochondria crosstalk; N,N-Dimethyltryptamine; Sigma-1 receptor, calcium homeostasis; cognitive impairment
    DOI:  https://doi.org/10.1186/s13195-024-01462-3
  6. Plant Commun. 2024 Apr 27. pii: S2590-3462(24)00199-8. [Epub ahead of print] 100929
    The VAMP-associated protein VAP27-1 plays a crucial role in plant resistance to ER stress by modulating ER-PM contact architecture in Arabidopsis.
    Yi Man, Yue Zhang, Linghui Chen, Junhui Zhou, Yufen Bu, Xi Zhang, Xiaojuan Li, Yun Li, Yanping Jing, Jinxing Lin.
      The endoplasmic reticulum (ER) and the plasma membrane (PM) form ER-PM contact sites (EPCSs) that allow the ER and PM to exchange material and information. Stress-induced disruption of protein folding triggers ER stress and the cell initiates the unfolded protein response (UPR) to resist the stress. However, whether EPCSs in plants play a role in ER stress remain unclear. VESICLE-ASSOCIATED MEMBRANE PROTEIN (VAMP)-ASSOCIATED PROTEIN 27-1 (VAP27-1) functions in EPCS tethering and is encoded by a family of ten genes (VAP27-1-10) in Arabidopsis thaliana. Here, we used CRISPR/Cas9-mediated genome editing to obtain a homozygous vap27-1 vap27-3 vap27-4 (vap27-1/3/4) triple mutant lacking three of the key VAP27 family members in Arabidopsis. The vap27-1/3/4 mutant exhibited defects in ER-PM connectivity and EPCS architecture, and excessive UPR signaling. We further showed that relocation of VAP27-1 to the PM mediates specific VAP27-1-related EPCS remodeling and expansion under ER stress. Moreover, the spatiotemporal dynamics of VAP27-1 at the PM increase ER-PM connectivity and enhance Arabidopsis resistance to ER stress. In addition, we uncovered an important role for intracellular calcium homeostasis in the regulation of UPR signaling. Taken together, our results broaden the understanding of the molecular and cellular mechanisms of ER stress and UPR signaling in plants, providing additional clues for improving plant broad-spectrum resistance to different stresses.
    Keywords:  Arabidopsis; ER stress; ER-PM contact sites; VAP27-1; unfolded protein response
    DOI:  https://doi.org/10.1016/j.xplc.2024.100929
  7. Biochem Biophys Res Commun. 2024 Apr 23. pii: S0006-291X(24)00516-3. [Epub ahead of print]715 149980
    Ceramide sorting into non-vesicular transport is independent of acyl chain length in budding yeast.
    Philipp Schlarmann, Kazuki Hanaoka, Atsuko Ikeda, Manuel Muñiz, Kouichi Funato.
      The transport of ceramide from the endoplasmic reticulum (ER) to the Golgi is a key step in the synthesis of complex sphingolipids, the main building blocks of the plasma membrane. In yeast, ceramide is transported to the Golgi either through ATP-dependent COPII vesicles of the secretory pathway or by ATP-independent non-vesicular transport that involves tethering proteins at ER-Golgi membrane contact sites. Studies in both mammalian and yeast cells reported that vesicular transport mainly carries ceramide containing very long chain fatty acids, while the main mammalian non-vesicular ceramide transport protein CERT only transports ceramides containing short chain fatty acids. However, if non-vesicular ceramide transport in yeast similarly favors short chain ceramides remained unanswered. Here we employed a yeast GhLag1 strain in which the endogenous ceramide synthase is replaced by the cotton-derived GhLag1 gene, resulting in the production of short chain C18 rather than C26 ceramides. We show that block of vesicular transport through ATP-depletion or the use of temperature-sensitive sec mutants caused a reduction in inositolphosphorylceramide (IPC) synthesis to similar extent in WT and GhLag1 backgrounds. Since the remaining IPC synthesis is a readout for non-vesicular ceramide transport, our results indicate that non-vesicular ceramide transport is neither blocked nor facilitated when only short chain ceramides are present. Therefore, we propose that the sorting of ceramide into non-vesicular transport is independent of acyl chain length in budding yeast.
    Keywords:  Acyl chain length; Budding yeast; Ceramide sorting; Endoplasmic reticulum; Golgi
    DOI:  https://doi.org/10.1016/j.bbrc.2024.149980
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