Nature Cell Biology

doi: 10.1038/s41556-018-0212-2pmid: 30258125

We are often asked about various aspects of the editor’s job, and most frequently about the editorial process after submission. Here, we outline what happens after a manuscript is submitted to the journal and clarify some misconceptions about the editorial process.

Flanagan, D.; Hodder, M.; Sansom, O.

doi: 10.1038/s41556-018-0210-4pmid: 30258126

Intra-tumour heterogeneity manifests both at the level of mutational burden, and at a functional level within genetically homogenous populations. A new modelling approach suggests stemness within colorectal tumours is defined by microenvironmental cues secreted from cancer-associated fibroblasts rather than cell-intrinsic properties.

Murphy, Michael

doi: 10.1038/s41556-018-0209-xpmid: 30224762

Ferroptosis is a regulated non-apoptotic form of cell death and its functional role in tumorigenesis remains elusive. A study now shows that the tumour suppressor BAP1 enhances ferroptosis by modulating expression of the cystine transporter SLC7A11, leading to improved control of tumour growth.

Hatzis, Pantelis; Snippert, Hugo

doi: 10.1038/s41556-018-0208-ypmid: 30258127

The intestinal crypt has become the prototype compartment to investigate adult stem cell biology, and the list of identified intestinal stem cell (ISC) markers is already extensive. A comprehensive study now uncovers an additional layer in ISC regulation by introducing long noncoding RNA lncGata6 to the stem cell repertoire.

Fox, Archa

doi: 10.1038/s41556-018-0207-zpmid: 30250063

Paraspeckles are nuclear bodies built on the long noncoding RNA, NEAT1, that regulate cellular homeostasis, but how they sense and help under stress is unclear. A study now shows mitochondrial stress modulates paraspeckles by altering NEAT1 expression with a feedback loop that influences mitochondrial homeostasis.

Doherty, Johnna; Baehrecke, Eric

doi: 10.1038/s41556-018-0201-5pmid: 30224761

Autophagy influences cell survival through maintenance of cell bioenergetics and clearance of protein aggregates and damaged organelles. Several lines of evidence indicate that autophagy is a multifaceted regulator of cell death, but controversy exists over whether autophagy alone can drive cell death under physiologically relevant circumstances. Here, we review the role of autophagy in cell death and examine how autophagy interfaces with other forms of cell death including apoptosis and necrosis.

Holcman, David; Parutto, Pierre; Chambers, Joseph; Fantham, Marcus; Young, Laurence; Marciniak, Stefan; Kaminski, Clemens; Ron, David; Avezov, Edward

doi: 10.1038/s41556-018-0192-2pmid: 30224760

The endoplasmic reticulum (ER), a network of membranous sheets and pipes, supports functions encompassing biogenesis of secretory proteins and delivery of functional solutes throughout the cell 1,2 . Molecular mobility through the ER network enables these functionalities, but diffusion alone is not sufficient to explain luminal transport across supramicrometre distances. Understanding the ER structure–function relationship is critical in light of mutations in ER morphology-regulating proteins that give rise to neurodegenerative disorders 3,4 . Here, super-resolution microscopy and analysis of single particle trajectories of ER luminal proteins revealed that the topological organization of the ER correlates with distinct trafficking modes of its luminal content: with a dominant diffusive component in tubular junctions and a fast flow component in tubules. Particle trajectory orientations resolved over time revealed an alternating current of the ER contents, while fast ER super-resolution identified energy-dependent tubule contraction events at specific points as a plausible mechanism for generating active ER luminal flow. The discovery of active flow in the ER has implications for timely ER content distribution throughout the cell, particularly important for cells with extensive ER-containing projections such as neurons.

Singh, Amrita; Saha, Tanumoy; Begemann, Isabell; Ricker, Andrea; Nüsse, Harald; Thorn-Seshold, Oliver; Klingauf, Jürgen; Galic, Milos; Matis, Maja

doi: 10.1038/s41556-018-0193-1pmid: 30202051

Coordinated rearrangements of cytoskeletal structures are the principal source of forces that govern cell and tissue morphogenesis 1,2 . However, unlike for actin-based mechanical forces, our knowledge about the contribution of forces originating from other cytoskeletal components remains scarce. Here, we establish microtubules as central components of cell mechanics during tissue morphogenesis. We find that individual cells are mechanically autonomous during early Drosophila wing epithelium development. Each cell contains a polarized apical non-centrosomal microtubule cytoskeleton that bears compressive forces, whereby acute elimination of microtubule-based forces leads to cell shortening. We further establish that the Fat planar cell polarity (Ft-PCP) signalling pathway 3,4 couples microtubules at adherens junctions (AJs) and patterns microtubule-based forces across a tissue via polarized transcellular stability, thus revealing a molecular mechanism bridging single cell and tissue mechanics. Together, these results provide a physical basis to explain how global patterning of microtubules controls cell mechanics to coordinate collective cell behaviour during tissue remodelling. These results also offer alternative paradigms towards the interplay of contractile and protrusive cytoskeletal forces at the single cell and tissue levels.

Zhu, Pingping; Wu, Jiayi; Wang, Yanying; Zhu, Xiaoxiao; Lu, Tiankun; Liu, Benyu; He, Luyun; Ye, Buqing; Wang, Shuo; Meng, Shu; Fan, Dongdong; Wang, Jing; Yang, Liuliu; Qin, Xiwen; Du, Ying; Li, Chong; He, Lei;

Wang, Yang; Hu, Shi-Bin; Wang, Meng-Ran; Yao, Run-Wen; Wu, Di; Yang, Li; Chen, Ling-Ling

doi: 10.1038/s41556-018-0204-2pmid: 30250064

The long noncoding RNA NEAT1 (nuclear enriched abundant transcript 1) nucleates the formation of paraspeckles, which constitute a type of nuclear body with multiple roles in gene expression. Here we identify NEAT1 regulators using an endogenous NEAT1 promoter-driven enhanced green fluorescent protein reporter in human cells coupled with genome-wide RNAi screens. The screens unexpectedly yield gene candidates involved in mitochondrial functions as essential regulators of NEAT1 expression and paraspeckle formation. Depletion of mitochondrial proteins and treatment of mitochondrial stressors both lead to aberrant NEAT1 expression via ATF2 as well as altered morphology and numbers of paraspeckles. These changes result in enhanced retention of mRNAs of nuclear-encoded mitochondrial proteins (mito-mRNAs) in paraspeckles. Correspondingly, NEAT1 depletion has profound effects on mitochondrial dynamics and function by altering the sequestration of mito-mRNAs in paraspeckles. Overall, our data provide a rich resource for understanding NEAT1 and paraspeckle regulation, and reveal a cross-regulation between paraspeckles and mitochondria.