bims-mecosi 2023-06-04 papers

Issue of 2023–06–04
five papers selected by
Verena Kohler, University of Graz

Exp Cell Res. 2023 May 26. pii: S0014-4827(23)00215-X. [Epub ahead of print] 113668

The ultrastructural function of MLN64 in the late endosome-mitochondria membrane contact sites in placental cells.

Atsuki Nara, Akimi Inoue, Yoshitaka Aoyama, Takashi Yazawa.

The close apposition between two different organelles is critical in essential processes such as ion homeostasis, signaling, and lipid transition. However, information related to the structural features of membrane contact sites (MCSs) is limited. This study used immuno-electron microscopy and immuno-electron tomography (I-ET) to analyze the two- and three-dimensional structures of the late endosome-mitochondria contact sites in placental cells. Filamentous structures or tethers were identified that connected the late endosomes and mitochondria. Lamp1 antibody-labeled I-ET revealed enrichment of tethers in the MCSs. The cholesterol-binding endosomal protein metastatic lymph node 64 (MLN64) encoded by STARD3 was required for the formation of this apposition. The distance of the late endosome-mitochondria contact sites was <20 nm, shorter than that in STARD3-knockdown cells (<150 nm). The perturbation of cholesterol egress from the endosomes induced by U18666A treatment produced a longer distance in the contact sites than that in knockdown cells. The late endosome-mitochondria tethers failed to form correctly in STARD3-knockdown cells. Our results unravel the role of MLN64 involved in MCSs between late endosomes and mitochondria in placental cells.

Keywords: Electron microscopy; Endosomes; MLN64; Membrane contact site; Organelle structure

DOI: https://doi.org/10.1016/j.yexcr.2023.113668

Curr Opin Cell Biol. 2023 May 26. pii: S0955-0674(23)00021-2. [Epub ahead of print]82 102172

New insights into the OSBP‒VAP cycle.

Mélody Subra, Bruno Antonny, Bruno Mesmin.

VAP-A is a major endoplasmic reticulum (ER) receptor that allows this organelle to engage numerous membrane contact sites with other organelles. One highly studied example is the formation of contact sites through VAP-A interaction with Oxysterol-binding protein (OSBP). This lipid transfer protein transports cholesterol from the ER to the trans-Golgi network owing to the counter-exchange of the phosphoinositide PI(4)P. In this review, we highlight recent studies that advance our understanding of the OSBP cycle and extend the model of lipid exchange to other cellular contexts and other physiological and pathological conditions.

DOI: https://doi.org/10.1016/j.ceb.2023.102172

Environ Sci Pollut Res Int. 2023 May 30.

Mitochondria-associated endoplasmic reticulum membranes participate mitochondrial dysfunction and endoplasmic reticulum stress caused by copper in duck kidney.

Junjun Peng, Xueyan Dai, Huiqin Fan, Chenghong Xing, Yu Zhuang, Xiaona Gao, Huabin Cao, Guoliang Hu, Fan Yang.

Copper (Cu) can be harmful to host physiology at high levels, although it is still unclear exactly how it causes nephrotoxicity. Mitochondrial dysfunction and endoplasmic reticulum (ER) stress are associated with heavy metal intoxication. Meanwhile, mitochondria and ER are connected via mitochondria-associated ER membranes (MAM). In order to reveal the crosstalk between them, a total of 144 1-day-old Peking ducks were randomly divided into four groups: control (basal diet), 100 mg/kg Cu, 200 mg/kg Cu, and 400 mg/kg Cu groups. Results found that excessive Cu disrupted MAM integrity, reduced the co-localization of IP3R and VDAC1, and significantly changed the MAM-related factors levels (Grp75, Mfn2, IP3R, MCU, PACS2, and VDAC1), leading to MAM dysfunction. We further found that Cu exposure induced mitochondrial dysfunction via decreasing the ATP level and the expression levels of COX4, TOM20, SIRT1, and OPA1 and up-regulating Parkin expression level. Meanwhile, Cu exposure dramatically increased the expression levels of Grp78, CRT, and ATF4, resulting in ER stress. Overall, these findings demonstrated MAM plays the critical role in Cu-induced kidney mitochondrial dysfunction and ER stress, which deepened our understanding of Cu-induced nephrotoxicity.

Keywords: Copper; Endoplasmic reticulum stress; Mitochondria-associated endoplasmic reticulum membrane; Mitochondrial dysfunction; Nephrotoxicity

DOI: https://doi.org/10.1007/s11356-023-27924-z

Front Neurosci. 2023 ;17 1198343

Mitochondria-associated endoplasmic reticulum membranes (MAMs) and their role in glaucomatous retinal ganglion cell degeneration-a mini review.

Jennifer H Pham, Dorota L Stankowska.

Glaucoma is a leading cause of blindness worldwide, commonly associated with elevated intraocular pressure (IOP), leading to degeneration of the optic nerve and death of retinal ganglion cells, the output neurons in the eye. In recent years, many studies have implicated mitochondrial dysfunction as a crucial player in glaucomatous neurodegeneration. Mitochondrial function has been an increasingly researched topic in glaucoma, given its vital role in bioenergetics and propagation of action potentials. One of the most metabolically active tissues in the body characterized by high oxygen consumption is the retina, particularly the retinal ganglion cells (RGCs). RGCs, which have long axons that extend from the eyes to the brain, rely heavily on the energy generated by oxidative phosphorylation for signal transduction, rendering them more vulnerable to oxidative damage. In various glaucoma models, mitochondrial dysfunction and stress from protein aggregates in the endoplasmic reticulum (ER) have been observed in the RGCs. However, it has been shown that the two organelles are connected through a network called mitochondria-associated ER membranes (MAMs); hence this crosstalk in a pathophysiological condition such as glaucoma should be evaluated. Here, we review the current literature suggestive of mitochondrial and ER stress related to glaucoma, indicating potential cross-signaling and the potential roles of MAMs.

Keywords: ER stress; MAMs; endoplasmic reticulum; glaucoma; inflammation; mitochondria; oxidative stress; retinal ganglion cells

DOI: https://doi.org/10.3389/fnins.2023.1198343

J Struct Biol. 2023 May 31. pii: S1047-8477(23)00045-X. [Epub ahead of print] 107982

Correlating cryo-super resolution radial fluctuations and dual-axis cryo-scanning transmission electron tomography to bridge the light-electron resolution gap.

Peter Kirchweger, Debakshi Mullick, Prabhu Prasad Swain, Sharon G Wolf, Michael Elbaum.

Visualization of organelles and their interactions with other features in the native cell remains a challenge in modern biology. We have introduced cryo-scanning transmission electron tomography (CSTET), which can access 3D volumes on the scale of 1 micron with a resolution of nanometers, making it ideal for this task. Here we introduce two relevant advances: a) we demonstrate the utility of multi-color super-resolution radial fluctuation light microscopy under cryogenic conditions (cryo-SRRF), and b) we extend the use of deconvolution processing for dual-axis CSTET data. We show that cryo-SRRF nanoscopy is able to reach resolutions in the range of 100 nm, using commonly available fluorophores and a conventional widefield microscope for cryo-correlative light-electron microscopy. Such resolution aids in precisely identifying regions of interest before tomographic acquisition and enhances precision in localizing features of interest within the 3D reconstruction. Dual-axis CSTET tilt series data and application of entropy regularized deconvolution during post-processing results in close-to-isotropic resolution in the reconstruction without averaging. The integration of cryo-SRRF with deconvolved dual-axis CSTET provides a versatile workflow for studying unique objects in a cell.

Keywords: CSTET; Cryo-CLEM; SRRF; cryo-ET; deconvolution; dual-axis tomography; mitochondria-ER contact site; mitochondrial matrix granule; super-resolution CLEM

DOI: https://doi.org/10.1016/j.jsb.2023.107982