bims-mecosi 2021-10-31 papers

Issue of 2021–10–31
four papers selected by
Verena Kohler, Stockholm University

J Cell Biol. 2021 Nov 01. pii: e202109021. [Epub ahead of print]220(11):

Cnm1: A bridge between mitochondria and nuclear ER.

Few membrane contact sites have been defined at the molecular level. By using a high-throughput, microscopy-based screen, Eisenberg-Bord, Zung et al. (2021. J. Cell Biol.https://doi.org/10.1083/jcb.202104100) identify Cnm1 as a novel tethering protein that mediates contact between mitochondria and the nuclear ER in response to phospholipid levels.

DOI: https://doi.org/10.1083/jcb.202109021

Int J Biochem Cell Biol. 2021 Oct 22. pii: S1357-2725(21)00182-5. [Epub ahead of print] 106101

It takes two to tango; the essential role of ER-mitochondrial contact sites in mitochondrial dynamics.

Irene M G M Hemel, Rita Sarantidou, Mike Gerards.

Mitochondria change their shape, size and number, in response to cellular demand, through mitochondrial dynamics. The interaction between mitochondria and the ER, through ER-mitochondrial contact sites, is crucial in mitochondrial dynamics. Several protein complexes tethering mitochondria to the ER include proteins involved in fission or fusion but also proteins involved in calcium homeostasis, which is known to affect mitochondrial dynamics. The formation of these contact sites are especially important for mitochondrial fission as these contact sites induce both outer and inner membrane constriction, prior to recruitment of Drp1. While the exact molecular mechanisms behind these constrictions remain uncertain, several hypotheses have been proposed. In this review, we discuss the involvement of tethering complexes in mitochondrial dynamics and provide an overview of the current knowledge and hypotheses on the constriction of the outer and inner mitochondrial membrane at ER-mitochondrial contact sites.

Keywords: ER-mitochondrial contact; Mitochondrial dynamics; Mitochondrial membrane constriction

DOI: https://doi.org/10.1016/j.biocel.2021.106101

J Cell Biol. 2021 Nov 01. pii: e202104100. [Epub ahead of print]220(11):

Cnm1 mediates nucleus-mitochondria contact site formation in response to phospholipid levels.

Michal Eisenberg-Bord, Naama Zung, Javier Collado, Layla Drwesh, Emma J Fenech, Amir Fadel, Nili Dezorella, Yury S Bykov, Doron Rapaport, Ruben Fernandez-Busnadiego, Maya Schuldiner.

Mitochondrial functions are tightly regulated by nuclear activity, requiring extensive communication between these organelles. One way by which organelles can communicate is through contact sites, areas of close apposition held together by tethering molecules. While many contacts have been characterized in yeast, the contact between the nucleus and mitochondria was not previously identified. Using fluorescence and electron microscopy in S. cerevisiae, we demonstrate specific areas of contact between the two organelles. Using a high-throughput screen, we uncover a role for the uncharacterized protein Ybr063c, which we have named Cnm1 (contact nucleus mitochondria 1), as a molecular tether on the nuclear membrane. We show that Cnm1 mediates contact by interacting with Tom70 on mitochondria. Moreover, Cnm1 abundance is regulated by phosphatidylcholine, enabling the coupling of phospholipid homeostasis with contact extent. The discovery of a molecular mechanism that allows mitochondrial crosstalk with the nucleus sets the ground for better understanding of mitochondrial functions in health and disease.

DOI: https://doi.org/10.1083/jcb.202104100

Traffic. 2021 Oct 24.

The E-Syt3 Cleavage and Traffic Uncovers the Primordial Cisterna, a New Organelle that Mothers the Lipid Droplets in the Adipocyte.

Vasiliki Lalioti, Galina V Beznoussenko, Alexander A Mironov, Ignacio V Sandoval.

Extended synaptotagmins are endoplasmic reticulum proteins consisting of an SMP domain and multiple C2 domains that bind phospholipids and Ca2+ . E-Syts create contact junctions between the ER and plasma membrane (PM) to facilitate the exchange of glycerophospholipids between the apposed membranes. We find in the differentiating adipocyte that the E-Syt3 carboxyl domain is cleaved by a multi-step mechanism that includes removing the C2C domain. Confocal and live-cell time-lapse studies show that truncated E-Syt3ΔC2C, as well as endogenous E-Syt3 and the coat protein PLIN1, target the LDs from an annular, single giant ER cisterna. Inhibition of the proteasome blocks the proteolytic cleavage of Esyt3 and E-Syt3ΔC2C and causes the E-Syt3ΔC2C retention in the giant cisterna. The Esyt3 and PLIN1 distributions and LDs biogenesis show that the primordial cisterna, as we call it, is the birth and nurturing site of LDs in the adipocyte. Isoproterenol-induced lipolysis results in loss of cytoplasmic LDs and reappearance of the primordial cisterna. Electron microscopy and 3D-electron tomography studies show that the primordial cisterna consists of a tightly-packed network of varicose tubules with extensively blistered membranes. Rounds of homotypic fusions from nascent to mature LDs play a central role in LD growth. The knockdown of E-Syt3 inhibits LD biogenesis. The identification of the primordial cisterna, an organelle that substitutes the randomly scattered ER foci that mother the LDs in non-adipose cells, sets the stage for a better understanding of LD biogenesis in the adipocyte.

Keywords: E-Syts; LD biogenesis; LD growth; Lipid droplets; Primordial Cisterna; Protein traffic

DOI: https://doi.org/10.1111/tra.12823