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Inter-organelle communication

Organelles have been traditionally viewed as individual entities with defined composition and organization that endow them with specialized functions. However, it is now apparent that intracellular membrane compartments engage in extensive communication, either indirectly, or directly through membrane contacts. Inter-organelle communication is essential for cell function and for tissue and organismal homeostasis, as it regulates processes from lipid metabolism to cell death.

This collection of research articles, reviews and protocols from across the Nature Research group showcases the latest progress in understanding the mechanisms and functions of inter-organelle communication. It also highlights how the recent characterization of membrane contact sites has established a new framework to study cellular processes in the context of physiology and disease.

Research articles

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.

Article | open | | Nature Communications

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.

Article | open | | Nature Communications

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.

Article | open | | Nature Communications

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.

Article | open | | Nature Communications

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.

Article | open | | Nature Communications

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.

Article | open | | Nature Communications

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.

Article | open | | Nature Communications

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.

Article | | Nature Plants

Reviews and protocols

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

Review Article | | Nature Reviews Molecular Cell Biology

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.

Review Article | | Nature Cell Biology

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.

Review Article | | Nature Reviews Cardiology

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.

Review Article | | Nature Reviews Molecular Cell Biology

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.

Review Article | | Nature Reviews Molecular Cell Biology