Inter-organelle communication

The internal organization of the cell has been enriched by the discovery that organelles establish membrane contact sites, however the entire repertoire of these contacts is still being explored. Here the authors systematically identify the landscape of cellular contact sites in yeast, discovering four potential novel contact sites and two tether proteins for the peroxisome-mitochondria contact site.

Formation of inter-organelle contacts between mitochondria and lysosomes, regulated by lysosomal RAB7 GTP hydrolysis, allows for bidirectional regulation of mitochondrial and lysosomal dynamics.

Using confocal and lattice light sheet microscopy, the authors perform systems-level analysis of the organelle interactome in live cells, allowing them to visualize the frequency and locality of up to five-way interactions between different organelles.

Shin et al. identify TBC1D23 as an adaptor that interacts both with golgins and endosomal WASH and is required for the delivery of endosome-derived vesicles to the trans-Golgi.

Lysosomal distribution is linked to the role of lysosomes in many cellular functions. Here the authors show that the lysosomal protein TMEM55B is regulated by TFEB and recruits JIP4 to the lysosomal surface inducing dynein-dependent transport of lysosomes toward the cell center in response to stress conditions.

Peroxisomes—tiny intracellular organelles that contain metabolic enzymes—are generated in mammalian cells by the fusion of structures that arise from both mitochondria and the endoplasmic reticulum.

Maillo et al. show that in hepatocytes ER stress upregulates CPEB4 through the UPR and circadian clock, leading to CPEB4-mediated translation for mitochondrial and ER homeostasis. CPEB4 loss leads to ageing- and high fat diet-induced liver steatosis.

ORP5/8 are endoplasmic reticulum (ER) membrane proteins implicated in lipid trafficking that localize to ER-plasma membrane (PM) contacts and maintain membrane homeostasis. Here the authors show that PtdIns(4,5)P ₂ plays a critical role in the targeting and function of ORP5/8 at the PM.

High-resolution images and tomography show unprecedented 3D structures of plasmodesmata. In cells just post-cytokinesis, plasmodesmata do not have a visible cytoplasmic sleeve but still conduct cell-to-cell movement of micro- and macromolecules.

Bcl-2 interacting killer (Bik) decreases airway epithelial hyperplasia via apoptosis mediated by calcium release from the endoplasmic reticulum (ER), but the mechanism is unclear. Here the authors show that Bik promotes Bak enrichment at the ER to tether mitochondria for efficient calcium transfer.

Fumagalli et al. show that Sec62 delivers ER components to the autolysosome for clearance by acting as a receptor for autophagy protein LC3-II. This identifies Sec62 as a critical factor for selective ER turnover.

Multiple plastid-derived signals have been proposed but not shown to move to the nucleus to promote plant acclimation to fluctuating light. Here the authors use a fluorescent hydrogen peroxide sensor to provide evidence that H₂O₂ is transferred directly from chloroplasts to nuclei to control nuclear gene expression.

The protein Mdm10 is known to be present in the endoplasmic reticulum-mitochondria encounter structure (ERMES) and in mitochondrial sorting and assembly machinery (SAM). Here, the authors examine how this protein interacts with SAM and EMRES, showing that the SAM-mediated protein machinery is independent of ERMES.

De Leo et al. identify a lysosomal response to autophagic cargo during lysosome–autophagosome fusion that involves TLR9 activation and OCRL recruitment, and leads to a regulated local increase in PtdIns(4,5)P₂, which is necessary for a normal autophagic flux.

Kopito and Schrul show that the peroxisome proteins PEX19 and PEX3 mediate the correct insertion of the lipid droplet protein UBXD8 into ER subdomains.

Orhon et al. report that primary-cilium-mediated fluid flow sensing triggers autophagy through LKB1–AMPK–mTOR signalling, and thereby controls the volume of kidney epithelial cells.

Autophagy requires transport of autophagosomes to the perinuclear region. Here, the authors show that ORP1L localizes to autophagosomes and mediates formation of ER contact sites that prevent autophagosome transport and fusion with endocytic vesicles when cholesterol levels are low.

Saheki and colleagues show that extended synaptotagmins (E-Syts), ER proteins that function as tethers to the plasma membrane, can transfer lipids between bilayers in a Ca²⁺- and SMP-domain-dependent manner, thus regulating plasma membrane lipid homeostasis.

The sorting of soluble proteins for degradation in the vacuole is of vital importance in plant cells, and relies on the activity of vacuolar sorting receptors (VSRs). Laboratory experiments with tobacco mesophyll protoplasts suggest that VSRs are required for the transport of ligands from the endoplasmic reticulum and Golgi to the trans-Golgi network/early endosome.

Cellular organelles extensively communicate with each other by close interactions, known as membrane contact sites. Schuldiner and Bohnert comment on the progress of this rapidly developing field, highlighting that the complexity of interactions at membrane contact sites is only now starting to emerge.

A class of probes enables highly multiplexed imaging and barcoding applications with Raman microscopy.

Cells activate a transcriptional response known as the mitochondrial unfolded protein response (UPR^mt) when mitochondrial integrity and function are impaired to promote their recovery. Recent insights into the regulation, mechanisms and functions of the UPR^mthave uncovered important links to ageing and ageing-associated diseases.

In this Review, Prinz and co-authors discuss the role of the endoplasmic reticulum (ER) in the de novo generation of peroxisomes, lipid droplets and omegasomes, and how this requires subdomains with specific protein and lipid compositions.

This protocol describes a substantially redeveloped approach for the localization of organelle proteins by isotope tagging (LOPIT) to enable subcellular localization of thousands of proteins per experiment (hyperLOPIT).

Mitochondrial metabolism is essential for the dynamic regulation of cardiac and vascular tissues, and the relevance of basic mitochondrial biology in cardiovascular disease is being increasingly recognized. In this Review, the authors explore the physical interaction between mitochondria and sarco/endoplasmic reticulum, discussing how the communication between these two organelles is involved in cardiovascular pathologies.

Signalling from the nucleus to mitochondria (NM signalling) is crucial for regulating mitochondrial function and ageing. It is initiated by nuclear DNA damage and controls genomic and mitochondrial integrity. Pharmacological modulation of NM signalling holds promise for improving lifespan and healthspan.

Cell Painting is a high-content screening assay that uses multiplexed fluorescent dyes for image-based profiling of ∼1,500 morphological features. Image analysis with CellProfiler automatically identifies and extracts data from individual cells.

As most mitochondrial proteins are encoded in the nucleus, mitochondrial activity requires efficient communication between the nuclear and mitochondrial genomes. This is mediated by nucleus-to-mitochondria (anterograde), mitochondria-to-nucleus (retrograde) and mitonuclear feedback signalling, as well as the integrated stress response and extracellular communication, which regulate homeostasis and, consequently, healthspan and lifespan.