Review

Authors: Simon Alberti, Amy Gladfelter, Tanja Mittag...

Evidence is now mounting that liquid-liquid phase separation (LLPS) underlies the formation of membraneless compartments in cells. This realization has motivated major efforts to delineate the function of such biomolecular condensates in normal cells and their roles in contexts ranging from development to age-related disease. There is great interest in understanding the underlying biophysical principles and the specific properties of biological condensates with the goal of bringing insights into a wide range of biological processes and systems. The explosion of physiological and pathological contexts involving LLPS requires clear standards for their study. Here, we propose guidelines for rigorous experimental characterization of LLPS processes in vitro and in cells, discuss the caveats of common experimental approaches, and point out experimental and theoretical gaps in the field.

Topics: Cell Physiological Phenomena; Liquid Phase Microextraction; Liquid-Liquid Extraction

PubMed: 30682370
DOI: 10.1016/j.cell.2018.12.035

Review

Authors: Giacomo Giuliani, Valter D Longo

Ketogenic diets (KDs), fasting, or prolonged physical activity elevate serum ketone bodies (KBs) levels, providing an alternative fuel source for the brain and other organs. However, KBs play pleiotropic roles that go beyond their role in energy production. KBs can act as signaling metabolites, influence gene expression, proteins' posttranslational modifications (PTMs), inflammation, and oxidative stress. Here, we explore the impact of KBs on mammalian cell physiology, including aging and tissue regeneration. We also concentrate on KBs and cancer, given the extensive evidence that dietary approaches inducing ketosis, including fasting-mimicking diets (FMDs) and KDs, can prevent cancer and affect tumor progression.

Topics: Animals; Humans; Ketone Bodies; Neoplasms; Brain; Oxidative Stress; Cell Physiological Phenomena; Mammals

PubMed: 38189128
DOI: 10.1152/ajpcell.00441.2023

Review

Authors: Daniel A Fletcher, R Dyche Mullins

The ability of a eukaryotic cell to resist deformation, to transport intracellular cargo and to change shape during movement depends on the cytoskeleton, an interconnected network of filamentous polymers and regulatory proteins. Recent work has demonstrated that both internal and external physical forces can act through the cytoskeleton to affect local mechanical properties and cellular behaviour. Attention is now focused on how cytoskeletal networks generate, transmit and respond to mechanical signals over both short and long timescales. An important insight emerging from this work is that long-lived cytoskeletal structures may act as epigenetic determinants of cell shape, function and fate.

Topics: Animals; Biomechanical Phenomena; Cell Physiological Phenomena; Cell Shape; Cytoskeleton; Epigenesis, Genetic; Humans

PubMed: 20110992
DOI: 10.1038/nature08908

Review

Authors: Sattar Taheri-Araghi, Steven D Brown, John T Sauls...

Single-cell techniques have a long history of unveiling fundamental paradigms in biology. Recent improvements in the throughput, resolution, and availability of microfluidics, computational power, and genetically encoded fluorescence have led to a modern renaissance in microbial physiology. This resurgence in research activity has offered new perspectives on physiological processes such as growth, cell cycle, and cell size of model organisms such as Escherichia coli. We expect these single-cell techniques, coupled with the molecular revolution of biology's recent half-century, to continue illuminating unforeseen processes and patterns in microorganisms, the bedrock of biological science. In this article we review major open questions in single-cell physiology, provide a brief introduction to the techniques for scientists of diverse backgrounds, and highlight some pervasive issues and their solutions.

Topics: Animals; Cell Physiological Phenomena; Escherichia coli; Microfluidics; Single-Cell Analysis

PubMed: 25747591
DOI: 10.1146/annurev-biophys-060414-034236

Review

Authors: Xuemin Wang, Christopher G Proud

Signaling through mammalian target of rapamycin (mTOR) is activated by amino acids, insulin, and growth factors, and impaired by nutrient or energy deficiency. mTOR plays key roles in cell physiology. mTOR regulates numerous components involved in protein synthesis, including initiation and elongation factors, and the biogenesis of ribosomes themselves.

Topics: Animals; Cell Physiological Phenomena; Humans; Protein Biosynthesis; Protein Kinases; Ribosomes; Signal Transduction; TOR Serine-Threonine Kinases

PubMed: 16990457
DOI: 10.1152/physiol.00024.2006

Authors: Josephine C Adams, Thordur Oskarsson

Topics: Cell Physiological Phenomena; Humans; Neoplasm Metastasis; Neoplasms

PubMed: 26428197
DOI: 10.1152/ajpcell.zh0-7813-editorial.2015

Review

Authors: Stephen H Wright

This brief review is intended to serve as a refresher on the ideas associated with teaching students the physiological basis of the resting membrane potential. The presentation is targeted toward first-year medical students, first-year graduate students, or senior undergraduates. The emphasis is on general concepts associated with generation of the electrical potential difference that exists across the plasma membrane of every animal cell. The intention is to provide students a general view of the quantitative relationship that exists between 1) transmembrane gradients for K(+) and Na(+) and 2) the relative channel-mediated permeability of the membrane to these ions.

Topics: Animals; Cell Physiological Phenomena; Electrophysiology; Humans; Membrane Potentials; Physiology

PubMed: 15545342
DOI: 10.1152/advan.00029.2004

Authors: Ulrich Blank, Carlo Pucillo

Topics: Humans; Mast Cells; Mastocytosis; Cell Physiological Phenomena

PubMed: 37928555
DOI: 10.3389/fimmu.2023.1303726

Review

Authors: David T McSwiggen, Mustafa Mir, Xavier Darzacq...

The idea that liquid-liquid phase separation (LLPS) may be a general mechanism by which molecules in the complex cellular milieu may self-organize has generated much excitement and fervor in the cell biology community. While this concept is not new, its rise to preeminence has resulted in renewed interest in the mechanisms that shape and drive diverse cellular self-assembly processes from gene expression to cell division to stress responses. In vitro biochemical data have been instrumental in deriving some of the fundamental principles and molecular grammar by which biological molecules may phase separate, and the molecular basis of these interactions. Definitive evidence is lacking as to whether the same principles apply in the physiological environment inside living cells. In this Perspective, we analyze the evidence supporting phase separation in vivo across multiple cellular processes. We find that the evidence for in vivo LLPS is often phenomenological and inadequate to discriminate between phase separation and other possible mechanisms. Moreover, the causal relationship and functional consequences of LLPS in vivo are even more elusive. We underscore the importance of performing quantitative measurements on proteins in their endogenous state and physiological abundance, as well as make recommendations for experiments that may yield more conclusive results.

Topics: Cell Biology; Cell Physiological Phenomena; Cytological Techniques; Fluorescence Recovery After Photobleaching; Gene Expression Regulation; Liquid-Liquid Extraction; Transcription Factors

PubMed: 31594803
DOI: 10.1101/gad.331520.119

Review

Authors: Yan G Zhao, Hong Zhang

In eukaryotic cells, various membrane-bound organelles compartmentalize diverse cellular activities in a spatially and temporally controlled manner. Numerous membraneless organelles assembled via liquid-liquid phase separation (LLPS), known as condensates, also facilitate compartmentalization of cellular functions. Emerging evidence shows that these two organelle types interact in many biological processes. Membranes modulate the biogenesis and dynamics of phase-separated condensates by serving as assembly platforms or by forming direct contacts. Phase separation of membrane-associated proteins participates in various trafficking events, such as clustering of vesicles for temporally controlled fusion and storage, and transport of membraneless condensates on membrane-bound organelles. Phase separation also acts in cargo trafficking pathways by sorting and docking cargos for translocon-mediated transport across membranes, by shuttling cargos through the nuclear pore complex, and by triggering the formation of surrounding autophagosomes for delivery to lysosomes. The coordinated actions of membrane-bound and membraneless organelles ensure spatiotemporal control of various cellular functions.

Topics: Autophagosomes; Biology; Biophysical Phenomena; Cell Physiological Phenomena; Humans; Membranes; Organelles

PubMed: 32726575
DOI: 10.1016/j.devcel.2020.06.033