Reviews & Analysis

ATPases transport ions into and out of cells to maintain ion concentration gradients and control aspects of the cellular environment, such as pH. Structural studies of the Na⁺,K⁺-ATPase, which transports Na⁺ and K⁺, and the H⁺-ATPase, which transports H⁺, have provided insights into their functions in eukaryotic cells.

Respiratory chain subunits are made up of proteins encoded by nuclear and mitochondrial DNA, which assemble to form functional enzymes. New findings reveal that the mitochondrial translation of Cox1, the core component of cytochromecoxidase, is directly coupled to the assembly of this respiratory complex.

Mitophagy is the selective elimination of mitochondria through autophagy. Recent studies have uncovered the molecular mechanisms mediating mitophagy in yeast and mammalian cells and have revealed that the dysregulation of one of these mechanisms — the PINK1–parkin-mediated signalling pathway — may contribute to Parkinson's disease.

There is increasing evidence that an 'open' chromatin state contributes to maintenance of pluripotency in stem cells, and that this requires regulation of both the global chromatin state and local repression of transcription. This regulation may also be relevant for chromatin control during reprogramming or during tumorigenesis.

In eukaryotes, the target of rapamycin (TOR) protein kinase simultaneously senses energy, nutrients and stress (and growth factors in metazoans) to regulate cell growth and division. Advances in our understanding of the regulation and functions of mammalian TOR (mTOR) are revealing its involvement in diabetes, cancer and ageing.

Mitochondria and chloroplasts import the vast majority of their proteins across two membranes. Although the import and initial sorting of precursor proteins is mediated by translocases that are functionally similiar in the outer membrane of both organelles, they each have a unique mode of translocation.

Conjugation of the ubiquitin-like protein SUMO to proteins regulates many biological processes. Insights are emerging into mechanisms that regulate the SUMO modification pathway, including other post-translational modifications. Many substrates also harbour additional characteristics that facilitate their modification.

The continuous fusion and fission of mitochondria is important for their inheritance and function. The core components of the fusion and fission machineries, and the mechanisms that regulate these processes, have recently been elucidated and found to be integral for the maintenance of cellular quality control.

Cells divide asymmetrically to generate diverse cell types during development. Research over the past 10 years has furthered our understanding of asymmetric cell division in invertebrates. Furthermore, this work has uncovered connections between asymmetric cell division and tumorigenesis and a role for this process in stem cell biology.

The MET receptor promotes tissue remodelling by integrating growth, survival and migration cues in response to environmental stimuli or cell-autonomous perturbations. The versatility of MET-mediated biological responses is sustained by qualitative and quantitative signal modulation, which can be exploited in regenerative medicine and cancer therapy.

Mammalian prions are typically associated with the development of neurodegenerative diseases. However, prions in fungi act as epigenetic determinants. The similarities between mammalian and fungal prions suggest that, rather than being a biological anomaly, prions might instead function as regulators of cell phenotype.

The mechanisms regulating the import of proteins into peroxisomes share surprising similarities with those controlling the degradation of proteins at the endoplasmic reticulum. These unexpected parallels may result from the common molecular machinery used to tag substrates and drive their removal from the membrane.

Transport protein particle (TRAPP; also known as trafficking protein particle) complexes activate the GTPase Ypt1 or RAB1 to regulate membrane traffic in yeast and mammals, respectively. Two different TRAPP complexes tether coated vesicles during endoplasmic reticulum–Golgi and intra-Golgi traffic, respectively, and a third complex functions in autophagy. The TRAPP complexes thereby connect GTPase activation to unique membrane-tethering events.

Organisms can anticipate environmental changes owing to an intrinsic molecular clock. Our molecular understanding of circadian oscillators has advanced over the past decade with the deployment of systems biology approaches, enabling a multiscale view of circadian systems from the molecular level to the intact organism.

Focal adhesion kinase (FAK) is a scaffold and tyrosine kinase protein that binds to itself and cellular partners through its four-point-one, ezrin, radixin, moesin (FERM) domain. Recent structural work reveals how regulatory proteins activate FAK by binding to its FERM domain, enabling it to coordinate diverse cellular responses.

Proteomes are typically analyzed by mass spectrometry, and recent advances have greatly increased the fraction of the proteome that can be identified and quantified in a single study. Mapping complete proteomes and using such maps for targeted quantitative proteomics will increase the impact of proteomics on biological and clinical research.

The aggregation of misfolded proteins is associated with the perturbation of cellular function and ageing. However, protein aggregation can also be a regulated process that deposits aggregates at specific cellular sites. This is protective as it facilitates aggregate solubilization, refolding and degradation by the protein quality-control network.

Metabolic pathways such as glycolysis and the pentose phosphate pathway communicate to cell cycle and apoptotic effectors, including D-type cyclins, CDKs, APC, p53, caspase 2 and BCL-2 proteins. The importance of this crosstalk is emphasized by the role of metabolic aberrations in the aetiology of disease.

In multicellular organisms, DNA replication adapts to variations in growth conditions, DNA damage and chromatin organization changes associated with cell differentiation. Therefore, only a subset of replication origins is used at each cell cycle, the choice of which is controlled by various factors including epigenetic mechanisms and gene expression.

Ten years ago, the cell biological role of lipid rafts was controversial owing to limited methodology and confusing nomenclature. Through technical advances, our concept of lipid rafts has evolved into that of dynamic nanoscale assemblies that can be stabilized to control signalling and membrane trafficking.