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Annu Rev Physiol 2020 02;82:485-506

Indiana Center for Musculoskeletal Health, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA; email:

Osteocytes are an ancient cell, appearing in fossilized skeletal remains of early fish and dinosaurs. Despite its relative high abundance, even in the context of nonskeletal cells, the osteocyte is perhaps among the least studied cells in all of vertebrate biology. Osteocytes are cells embedded in bone, able to modify their surrounding extracellular matrix via specialized molecular remodeling mechanisms that are independent of the bone forming osteoblasts and bone-resorbing osteoclasts. Read More

Annu Rev Physiol 2020 02;82:63-78

Center for Cardiovascular Research, John A. Burns School of Medicine, University of Hawaii at Manoa, Honolulu, Hawaii 96813, USA; email:

Cardiac fibrosis is a pathological condition that occurs after injury and during aging. Currently, there are limited means to effectively reduce or reverse fibrosis. Key to identifying methods for curbing excess deposition of extracellular matrix is a better understanding of the cardiac fibroblast, the cell responsible for collagen production. Read More

Annu Rev Physiol 2020 02 22;82:21-43. Epub 2019 Nov 22.

Department of Physiology and Biophysics, University of Colorado Anschutz Medical Campus, Aurora, Colorado 80045, USA; email:

A progressive decline in maximum heart rate (mHR) is a fundamental aspect of aging in humans and other mammals. This decrease in mHR is independent of gender, fitness, and lifestyle, affecting in equal measure women and men, athletes and couch potatoes, spinach eaters and fast food enthusiasts. Importantly, the decline in mHR is the major determinant of the age-dependent decline in aerobic capacity that ultimately limits functional independence for many older individuals. Read More

Annu Rev Physiol 2020 02 19;82:365-390. Epub 2019 Nov 19.

Division of Nephrology, Department of Medicine, Duke University School of Medicine, Durham, North Carolina 27710, USA; email:

Chronic kidney disease (CKD) is a global health epidemic that accelerates cardiovascular disease, increases risk of infection, and causes anemia and bone disease, among other complications that collectively increase risk of premature death. Alterations in calcium and phosphate homeostasis have long been considered nontraditional risk factors for many of the most morbid outcomes of CKD. The discovery of fibroblast growth factor 23 (FGF23), which revolutionized the diagnosis and treatment of rare hereditary disorders of FGF23 excess that cause hypophosphatemic rickets, has also driven major paradigm shifts in our understanding of the pathophysiology and downstream end-organ complications of disordered mineral metabolism in CKD. Read More

Annu Rev Physiol 2020 02 18;82:177-202. Epub 2019 Nov 18.

Department of Medical Genetics, University of Calgary, Calgary, Alberta T2N 4N1, Canada; email:

Endocrine disrupting chemicals are common in our environment and act on hormone systems and signaling pathways to alter physiological homeostasis. Gestational exposure can disrupt developmental programs, permanently altering tissues with impacts lasting into adulthood. The brain is a critical target for developmental endocrine disruption, resulting in altered neuroendocrine control of hormonal signaling, altered neurotransmitter control of nervous system function, and fundamental changes in behaviors such as learning, memory, and social interactions. Read More

Annu Rev Physiol 2020 02 15;82:103-126. Epub 2019 Nov 15.

Department of Biology, University of Copenhagen, DK-2100 Copenhagen, Denmark; email:

Acidic metabolic waste products accumulate in the tumor microenvironment because of high metabolic activity and insufficient perfusion. In tumors, the acidity of the interstitial space and the relatively well-maintained intracellular pH influence cancer and stromal cell function, their mutual interplay, and their interactions with the extracellular matrix. Tumor pH is spatially and temporally heterogeneous, and the fitness advantage of cancer cells adapted to extracellular acidity is likely particularly evident when they encounter less acidic tumor regions, for instance, during invasion. Read More

Annu Rev Physiol 2020 02 15;82:413-431. Epub 2019 Nov 15.

Channing Division of Network Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA; email:

Although chronic obstructive pulmonary disease (COPD) risk is strongly influenced by cigarette smoking, genetic factors are also important determinants of COPD. In addition to Mendelian syndromes such as alpha-1 antitrypsin deficiency, many genomic regions that influence COPD susceptibility have been identified in genome-wide association studies. Similarly, multiple genomic regions associated with COPD-related phenotypes, such as quantitative emphysema measures, have been found. Read More

Annu Rev Physiol 2020 02 15;82:151-176. Epub 2019 Nov 15.

Laboratory of Cell Calcium Signaling, Shanghai Institute for Advanced Immunochemical Studies (SIAIS), ShanghaiTech University, Shanghai, 201210, China; email:

In the body, extracellular stimuli produce inositol 1,4,5-trisphosphate (IP), an intracellular chemical signal that binds to the IP receptor (IPR) to release calcium ions (Ca) from the endoplasmic reticulum. In the past 40 years, the wide-ranging functions mediated by IPR and its genetic defects causing a variety of disorders have been unveiled. Recent cryo-electron microscopy and X-ray crystallography have resolved IPR structures and begun to integrate with concurrent functional studies, which can explicate IP-dependent opening of Ca-conducting gates placed ∼90 Å away from IP-binding sites and its regulation by Ca. Read More

Annu Rev Physiol 2020 02 15;82:433-459. Epub 2019 Nov 15.

Division of Pulmonary and Critical Care Medicine, Department of Medicine, Weill Cornell Medicine, New York, NY 10065, USA; email:

People worldwide are living longer, and it is estimated that by 2050, the proportion of the world's population over 60 years of age will nearly double. Natural lung aging is associated with molecular and physiological changes that cause alterations in lung function, diminished pulmonary remodeling and regenerative capacity, and increased susceptibility to acute and chronic lung diseases. As the aging population rapidly grows, it is essential to examine how alterations in cellular function and cell-to-cell interactions of pulmonary resident cells and systemic immune cells contribute to a higher risk of increased susceptibility to infection and development of chronic diseases, such as chronic obstructive pulmonary disease and interstitial pulmonary fibrosis. Read More

Annu Rev Physiol 2020 02 11;82:323-342. Epub 2019 Nov 11.

Division of Nephrology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215, USA; email:

Genetic variants in the gene, found only in individuals of recent African ancestry, greatly increase risk of multiple types of kidney disease. These kidney risk alleles are a rare example of genetic variants that are common but also have a powerful effect on disease susceptibility. These alleles rose to high frequency in sub-Saharan Africa because they conferred protection against pathogenic trypanosomes that cause African sleeping sickness. Read More

Annu Rev Physiol 2020 02 8;82:461-484. Epub 2019 Nov 8.

Center for Clinical and Translational Research, Maine Medical Center Research Institute, Scarborough, Maine 04074, USA; email:

The skeleton harbors an array of lineage cells that have an essential role in whole body homeostasis. Adipocytes start the colonization of marrow space early in postnatal life, expanding progressively and influencing other components of the bone marrow through paracrine signaling. In this unique, closed, and hypoxic environment close to the endosteal surface and adjacent to the microvascular space the marrow adipocyte can store or provide energy, secrete adipokines, and target neighboring bone cells. Read More

Annu Rev Physiol 2020 02 28;82:1-20. Epub 2019 Oct 28.

Department of Medicine, Washington University School of Medicine, St. Louis, Missouri 63110, USA; email:

Despite mounting evidence implicating inflammation in cardiovascular diseases, attempts at clinical translation have shown mixed results. Recent preclinical studies have reenergized this field and provided new insights into how to favorably modulate cardiac macrophage function in the context of acute myocardial injury and chronic disease. In this review, we discuss the origins and roles of cardiac macrophage populations in the steady-state and diseased heart, focusing on the human heart and mouse models of ischemia, hypertensive heart disease, and aortic stenosis. Read More

Annu Rev Physiol 2020 02 22;82:297-322. Epub 2019 Oct 22.

Joan and Sanford I. Weill Department of Medicine, Division of Nephrology and Hypertension, Weill Cornell Medicine, New York, NY 10065, USA; email:

Autophagy is a cellular homeostatic program for the turnover of cellular organelles and proteins, in which double-membraned vesicles (autophagosomes) sequester cytoplasmic cargos, which are subsequently delivered to the lysosome for degradation. Emerging evidence implicates autophagy as an important modulator of human disease. Macroautophagy and selective autophagy (e. Read More

Annu Rev Physiol 2020 02 21;82:227-249. Epub 2019 Oct 21.

Department of Molecular and Integrative Physiology and the Geriatrics Center, University of Michigan, Ann Arbor, Michigan 48109, USA; email:

Sensory neurons provide organisms with data about the world in which they live, for the purpose of successfully exploiting their environment. The consequences of sensory perception are not simply limited to decision-making behaviors; evidence suggests that sensory perception directly influences physiology and aging, a phenomenon that has been observed in animals across taxa. Therefore, understanding the neural mechanisms by which sensory input influences aging may uncover novel therapeutic targets for aging-related physiologies. Read More

Annu Rev Physiol 2020 02 21;82:343-363. Epub 2019 Oct 21.

Division of Nephrology, Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama 35233, USA; email:

Many physiological processes, including most kidney-related functions, follow specific rhythms tied to a 24-h cycle. This is largely because circadian genes operate in virtually every cell type in the body. In addition, many noncanonical genes have intrinsic circadian rhythms, especially within the liver and kidney. Read More

Annu Rev Physiol 2020 02 16;82:251-273. Epub 2019 Oct 16.

Division of Digestive and Liver Diseases, Department of Medicine, Columbia University, New York, NY 10032, USA; email:

The bone morphogenetic protein (BMP) pathway is essential for the morphogenesis of multiple organs in the digestive system. Abnormal BMP signaling has also been associated with disease initiation and progression in the gastrointestinal (GI) tract and associated organs. Recent studies using animal models, tissue organoids, and human pluripotent stem cells have significantly expanded our understanding of the roles played by BMPs in the development and homeostasis of GI organs. Read More

Annu Rev Physiol 2020 02 16;82:127-149. Epub 2019 Oct 16.

Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, Sevilla 41013, Spain; email:

The carotid body (CB) is an arterial chemoreceptor organ located in the carotid bifurcation and has a well-recognized role in cardiorespiratory regulation. The CB contains neurosecretory sensory cells (glomus cells), which release transmitters in response to hypoxia, hypercapnia, and acidemia to activate afferent sensory fibers terminating in the respiratory and autonomic brainstem centers. Knowledge of the physiology of the CB has progressed enormously in recent years. Read More

Annu Rev Physiol 2020 02 16;82:275-295. Epub 2019 Oct 16.

Departments of Internal Medicine, Neuroscience, and Pharmacology, Francois M. Abboud Cardiovascular Center, Carver College of Medicine, University of Iowa, Iowa City, Iowa 52242, USA; email:

Cerebral small vessel disease (SVD) is characterized by changes in the pial and parenchymal microcirculations. SVD produces reductions in cerebral blood flow and impaired blood-brain barrier function, which are leading contributors to age-related reductions in brain health. End-organ effects are diverse, resulting in both cognitive and noncognitive deficits. Read More

Annu Rev Physiol 2020 02 14;82:203-226. Epub 2019 Oct 14.

Immunology Discovery, Genentech, Inc., South San Francisco, California 94080, USA; email:

Regenerative processes that maintain the function of the gastrointestinal (GI) epithelium are critical for health and survival of multicellular organisms. In insects and vertebrates, intestinal stem cells (ISCs) regenerate the GI epithelium. ISC function is regulated by intrinsic, local, and systemic stimuli to adjust regeneration to tissue demands. Read More

Annu Rev Physiol 2020 02 7;82:79-101. Epub 2019 Oct 7.

Division of Cardiovascular Diseases, Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama 35294, USA; email:

On Earth, all life is exposed to dramatic changes in the environment over the course of the day; consequently, organisms have evolved strategies to both adapt to and anticipate these 24-h oscillations. As a result, time of day is a major regulator of mammalian physiology and processes, including transcription, signaling, metabolism, and muscle contraction, all of which oscillate over the course of the day. In particular, the heart is subject to wide fluctuations in energetic demand throughout the day as a result of waking, physical activity, and food intake patterns. Read More

Annu Rev Physiol 2020 02 4;82:45-61. Epub 2019 Oct 4.

Department of Regenerative Medicine and Cell Biology and Department of Medicine Division of Cardiology, Medical University of South Carolina, Charleston, South Carolina 29425, USA; email:

In mammals, most cardiomyocytes (CMs) become polyploid (they have more than two complete sets of chromosomes). The purpose of this review is to evaluate assumptions about CM ploidy that are commonly discussed, even if not experimentally demonstrated, and to highlight key issues that are still to be resolved. Topics discussed here include () technical and conceptual difficulties in defining a polyploid CM, () the candidate role of reactive oxygen as a proximal trigger for the onset of polyploidy, () the relationship between polyploidization and other aspects of CM maturation, () recent insights related to the regenerative role of the subpopulation of CMs that are not polyploid, and () speculations as to why CMs become polyploid at all. Read More

Annu Rev Physiol 2020 02 27;82:391-412. Epub 2019 Sep 27.

Division of Pulmonary and Critical Care Medicine, Washington University School of Medicine, St. Louis, Missouri 63110, USA; email:

Circadian rhythms are daily cycles in biological function that are ubiquitous in nature. Understood as a means for organisms to anticipate daily environmental changes, circadian rhythms are also important for orchestrating complex biological processes such as immunity. Nowhere is this more evident than in the respiratory system, where circadian rhythms in inflammatory lung disease have been appreciated since ancient times. Read More

Annu Rev Physiol 2020 02 25;82:507-529. Epub 2019 Sep 25.

Bone Cell Biology and Disease Unit, St. Vincent's Institute of Medical Research, Melbourne, Victoria 3065, Australia; email:

Bone remodeling is essential for the repair and replacement of damaged and old bone. The major principle underlying this process is that osteoclast-mediated resorption of a quantum of bone is followed by osteoblast precursor recruitment; these cells differentiate to matrix-producing osteoblasts, which form new bone to replace what was resorbed. Evidence from osteopetrotic syndromes indicate that osteoclasts not only resorb bone, but also provide signals to promote bone formation. Read More

Annu Rev Physiol 2019 02;81:335-357

Murdoch Children's Research Institute, Parkville, Victoria 3052, Australia; email:

Human kidney tissue can now be generated via the directed differentiation of human pluripotent stem cells. This advance is anticipated to facilitate the modeling of human kidney diseases, provide platforms for nephrotoxicity screening, enable cellular therapy, and potentially generate tissue for renal replacement. All such applications will rely upon the accuracy and reliability of the model and the capacity for stem cell-derived kidney tissue to recapitulate both normal and diseased states. Read More

Annu Rev Physiol 2019 02;81:113-137

Department of Anesthesiology, Washington University School of Medicine, St. Louis, Missouri 63110, USA; email:

Ca- and voltage-gated K channels of large conductance (BK channels) are expressed in a diverse variety of both excitable and inexcitable cells, with functional properties presumably uniquely calibrated for the cells in which they are found. Although some diversity in BK channel function, localization, and regulation apparently arises from cell-specific alternative splice variants of the single pore-forming α subunit ( KCa1.1, Kcnma1, Slo1) gene, two families of regulatory subunits, β and γ, define BK channels that span a diverse range of functional properties. Read More

Annu Rev Physiol 2019 02;81:483-503

State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou 510060, China; email: ,

Endothelial cell (EC) metabolism is important for health and disease. Metabolic pathways, such as glycolysis, fatty acid oxidation, and amino acid metabolism, determine vasculature formation. These metabolic pathways have different roles in securing the production of energy and biomass and the maintenance of redox homeostasis in vascular migratory tip cells, proliferating stalk cells, and quiescent phalanx cells, respectively. Read More

Annu Rev Physiol 2019 02;81:429-452

Medical Research Council, Laboratory of Molecular Biology, Cambridge University, Cambridgeshire CB2 0QH, United Kingdom; email:

Although, as the major organ of gas exchange, the lung is considered a nonlymphoid organ, an interconnected network of lung-resident innate cells, including epithelial cells, dendritic cells, macrophages, and natural killer cells is crucial for its protection. These cells provide defense against a daily assault by airborne bacteria, viruses, and fungi, as well as prevent the development of cancer, allergy, and the outgrowth of commensals. Our understanding of this innate immune environment has recently changed with the discovery of a family of innate lymphoid cells (ILCs): ILC1s, ILC2s, and ILC3s. Read More

Annu Rev Physiol 2019 02;81:359-373

University of Montreal and Nephrology Service, Research Center, Hôpital du Sacré-Coeur de Montreal, Montreal, Quebec H4J 1C5, Canada; email:

Recent experiments using optogenetic tools facilitate the identification and functional analysis of thirst neurons and vasopressin-producing neurons. Four major advances provide a detailed anatomy and physiology of thirst, taste for water, and arginine-vasopressin (AVP) release: ( a) Thirst and AVP release are regulated by the classical homeostatic, interosensory plasma osmolality negative feedback as well as by novel, exterosensory, anticipatory signals. These anticipatory signals for thirst and vasopressin release concentrate on the same homeostatic neurons and circumventricular organs that monitor the composition of blood. Read More

Annu Rev Physiol 2019 02;81:89-111

Department of Biology, Ecology and Earth Science, University of Calabria, 87036 Arcavacata di Rende (CS), Italy.

Maternal cardiovascular changes during pregnancy include an expansion of plasma volume, increased cardiac output, decreased peripheral resistance, and increased uteroplacental blood flow. These adaptations facilitate the progressive increase in uteroplacental perfusion that is required for normal fetal growth and development, prevent the development of hypertension, and provide a reserve of blood in anticipation of the significant blood loss associated with parturition. Each woman's genotype and phenotype determine her ability to adapt in response to molecular signals that emanate from the fetoplacental unit. Read More

Annu Rev Physiol 2019 02;81:309-333

Division of Nephrology, Johns Hopkins School of Medicine, Baltimore, Maryland 21287, USA; email:

The current unidimensional paradigm of kidney disease detection is incompatible with the complexity and heterogeneity of renal pathology. The diagnosis of kidney disease has largely focused on glomerular filtration, while assessment of kidney tubular health has notably been absent. Following insult, the kidney tubular cells undergo a cascade of cellular responses that result in the production and accumulation of low-molecular-weight proteins in the urine and systemic circulation. Read More

Annu Rev Physiol 2019 02;81:505-534

Edwin L. Steele Laboratory, Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114, USA; email:

Abnormal blood and lymphatic vessels create a hostile tumor microenvironment characterized by hypoxia, low pH, and elevated interstitial fluid pressure. These abnormalities fuel tumor progression, immunosuppression, and treatment resistance. In 2001, we proposed a novel hypothesis that the judicious use of antiangiogenesis agents-originally developed to starve tumors-could transiently normalize tumor vessels and improve the outcome of anticancer drugs administered during the window of normalization. Read More

Annu Rev Physiol 2019 02;81:535-560

VIB-Center for Cancer Biology and Department of Oncology, KU Leuven, Leuven B-3000 Belgium; email:

Research over the last decades has provided strong evidence for the pivotal role of the tumor-associated blood and lymphatic vasculature in supporting immunoevasion and in subverting T cell-mediated immunosurveillance. Conversely, tumor blood and lymphatic vessel growth is in part regulated by the immune system, with infiltrating innate as well as adaptive immune cells providing both immunosuppressive and various angiogenic signals. Thus, tumor angiogenesis and escape of immunosurveillance are two cancer hallmarks that are tightly linked and interregulated by cell constituents from compartments secreting both chemokines and cytokines. Read More

Annu Rev Physiol 2019 02 10;81:607-627. Epub 2018 Dec 10.

Centre of Inflammation and Metabolism/Centre for Physical Activity Research (CIM/CFAS), Rigshospitalet, University of Copenhagen, DK-2100 Copenhagen, Denmark; email:

Physical inactivity is one of the leading health problems in the world. Strong epidemiological and clinical evidence demonstrates that exercise decreases the risk of more than 35 different disorders and that exercise should be prescribed as medicine for many chronic diseases. The physiology and molecular biology of exercise suggests that exercise activates multiple signaling pathways of major health importance. Read More

Annu Rev Physiol 2019 02 28;81:375-402. Epub 2018 Nov 28.

Department of Medicine, Yale School of Medicine, New Haven, Connecticut 06520, USA; email:

Regulated cell death is a major mechanism to eliminate damaged, infected, or superfluous cells. Previously, apoptosis was thought to be the only regulated cell death mechanism; however, new modalities of caspase-independent regulated cell death have been identified, including necroptosis, pyroptosis, and autophagic cell death. As an understanding of the cellular mechanisms that mediate regulated cell death continues to grow, there is increasing evidence that these pathways are implicated in the pathogenesis of many pulmonary disorders. Read More

Annu Rev Physiol 2019 02 28;81:453-482. Epub 2018 Nov 28.

Division of Pulmonary and Critical Care Medicine, Weill Cornell Medicine, New York, NY 10065, USA; email:

Mitochondria are an iconic distinguishing feature of eukaryotic cells. Mitochondria encompass an active organellar network that fuses, divides, and directs a myriad of vital biological functions, including energy metabolism, cell death regulation, and innate immune signaling in different tissues. Another crucial and often underappreciated function of these dynamic organelles is their central role in the metabolism of the most abundant and biologically versatile transition metals in mammalian cells, iron. Read More

Annu Rev Physiol 2019 02 28;81:139-164. Epub 2018 Nov 28.

Cardiovascular Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA; email:

Branched chain amino acids (BCAAs) are building blocks for all life-forms. We review here the fundamentals of BCAA metabolism in mammalian physiology. Decades of studies have elicited a deep understanding of biochemical reactions involved in BCAA catabolism. Read More

Annu Rev Physiol 2019 02 28;81:403-428. Epub 2018 Nov 28.

Center for Translational Medicine and Jane and Leonard Korman Lung Center, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA; email:

The lung is often overlooked as a metabolically active organ, yet biochemical studies have long demonstrated that glucose utilization surpasses that of many other organs, including the heart, kidney, and brain. For most cells in the lung, energy consumption is relegated to performing common cellular tasks, like mRNA transcription and protein translation. However, certain lung cell populations engage in more specialized types of energy-consuming behaviors, such as the beating of cilia or the production of surfactant. Read More

Annu Rev Physiol 2019 02 12;81:211-233. Epub 2018 Nov 12.

Department of Surgery, University of Michigan, Ann Arbor, Michigan 48109, USA; email:

Pancreatic cancer is characterized by an extensive fibroinflammatory reaction that includes immune cells, fibroblasts, extracellular matrix, vascular and lymphatic vessels, and nerves. Overwhelming evidence indicates that the pancreatic cancer microenvironment regulates cancer initiation, progression, and maintenance. Pancreatic cancer treatment has progressed little over the past several decades, and the prognosis remains one of the worst for any cancer. Read More

Annu Rev Physiol 2019 02 7;81:585-605. Epub 2018 Nov 7.

Mechanobiology Institute, National University of Singapore, Singapore 117411, Singapore; email:

It is increasingly clear that mechanotransduction pathways play important roles in regulating fundamental cellular functions. Of the basic mechanical functions, the determination of cellular morphology is critical. Cells typically use many mechanosensitive steps and different cell states to achieve a polarized shape through repeated testing of the microenvironment. Read More

Annu Rev Physiol 2019 02 31;81:235-259. Epub 2018 Oct 31.

Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA; email:

At the most fundamental level, the bowel facilitates absorption of small molecules, regulates fluid and electrolyte flux, and eliminates waste. To successfully coordinate this complex array of functions, the bowel relies on the enteric nervous system (ENS), an intricate network of more than 500 million neurons and supporting glia that are organized into distinct layers or plexi within the bowel wall. Neuron and glial diversity, as well as neurotransmitter and receptor expression in the ENS, resembles that of the central nervous system. Read More

Annu Rev Physiol 2019 02 31;81:165-188. Epub 2018 Oct 31.

Department of Pathology and Laboratory Medicine, Molecular Biology Institute, David Geffen School of Medicine, University of California, Los Angeles, California 90272, USA; email:

Phospholipids are major constituents of biological membranes. The fatty acyl chain composition of phospholipids determines the biophysical properties of membranes and thereby affects their impact on biological processes. The composition of fatty acyl chains is also actively regulated through a deacylation and reacylation pathway called Lands' cycle. Read More

Annu Rev Physiol 2019 02 31;81:261-284. Epub 2018 Oct 31.

Visceral Pain Research Group, College of Medicine and Public Health, Centre for Neuroscience, Flinders University, Bedford Park, South Australia 5042, Australia; email:

Most of us live blissfully unaware of the orchestrated function that our internal organs conduct. When this peace is interrupted, it is often by routine sensations of hunger and urge. However, for >20% of the global population, chronic visceral pain is an unpleasant and often excruciating reminder of the existence of our internal organs. Read More

Annu Rev Physiol 2019 02 24;81:189-209. Epub 2018 Oct 24.

Department of Pathology, University of Michigan, Ann Arbor, Michigan 48109, USA; email: ,

The gastrointestinal mucosa, structurally formed by the epithelium and lamina propria, serves as a selective barrier that separates luminal contents from the underlying tissues. Gastrointestinal mucosal wound repair is orchestrated by a series of spatial and temporal events that involve the epithelium, recruited immune cells, resident stromal cells, and the microbiota present in the wound bed. Upon injury, repair of the gastrointestinal barrier is mediated by collective migration, proliferation, and subsequent differentiation of epithelial cells. Read More

Annu Rev Physiol 2019 02 24;81:43-62. Epub 2018 Oct 24.

Department of Molecular and Cell Biology, University of Leicester, Leicester LE1 7RH, United Kingdom; email:

In the nervous system, ATP is co-stored in vesicles with classical transmitters and released in a regulated manner. ATP from the intracellular compartment can also exit the cell through hemichannels and following shear stress or membrane damage. In the past 30 years, the action of ATP as an extracellular transmitter at cell-surface receptors has evolved from somewhat of a novelty that was treated with skepticism to purinergic transmission being accepted as having widespread important functional roles mediated by ATP-gated ionotropic P2X receptors (P2XRs). Read More

Annu Rev Physiol 2019 02 26;81:561-583. Epub 2018 Sep 26.

Department of Biology, McMaster University, Hamilton, Ontario L8S 4K1, Canada; email:

Comparative physiology studies of high-altitude species provide an exceptional opportunity to understand naturally evolved mechanisms of hypoxia resistance. Aerobic capacity (VOmax) is a critical performance trait under positive selection in some high-altitude taxa, and several high-altitude natives have evolved to resist the depressive effects of hypoxia on VOmax. This is associated with enhanced flux capacity through the O transport cascade and attenuation of the maladaptive responses to chronic hypoxia that can impair O transport. Read More

Annu Rev Physiol 2019 02 26;81:285-308. Epub 2018 Sep 26.

Department of Integrative Physiology, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan.

Maintenance of a homeostatic body core temperature is a critical brain function accomplished by a central neural network. This orchestrates a complex behavioral and autonomic repertoire in response to environmental temperature challenges or declining energy homeostasis and in support of immune responses and many behavioral states. This review summarizes the anatomical, neurotransmitter, and functional relationships within the central neural network that controls the principal thermoeffectors: cutaneous vasoconstriction regulating heat loss and shivering and brown adipose tissue for heat production. Read More

Annu Rev Physiol 2019 02 26;81:1-17. Epub 2018 Sep 26.

Center for Pharmacogenomics, Department of Internal Medicine, Washington University School of Medicine, St. Louis, Missouri 63110, USA; email:

The concept that mitochondria are highly dynamic is as widely accepted as it is untrue for a number of important contexts. Healthy mitochondria of the most energy-dependent and mitochondrial-rich mammalian organ, the heart, only rarely undergo fusion or fission and are seemingly static within cardiac myocytes. Here, we revisit mitochondrial dynamism with a fresh perspective developed from the recently discovered multifunctionality of mitochondrial fusion proteins and newly defined mechanisms for direct cross talk between mitochondrial dynamics, biogenesis, quality control, and trafficking pathways. Read More

Annu Rev Physiol 2019 02 14;81:63-87. Epub 2018 Sep 14.

King's College London, School of Cardiovascular Medicine and Sciences, The British Heart Foundation Centre of Excellence, The Rayne Institute, St. Thomas' Hospital, London SE1 7EH, United Kingdom; email:

Oxidant molecules are produced in biological systems and historically have been considered causal mediators of damage and disease. While oxidants may contribute to the pathogenesis of disease, evidence continues to emerge that shows these species also play important regulatory roles in health. A major mechanism of oxidant sensing and signaling involves their reaction with reactive cysteine thiols within proteins, inducing oxidative posttranslational modifications that can couple to altered function to enable homeostatic regulation. Read More

Annu Rev Physiol 2019 02 14;81:19-41. Epub 2018 Sep 14.

Muscle Health Research Centre, School of Kinesiology and Health Science, York University, Toronto, Ontario, M3J 1P3, Canada; email:

Mitochondria are critical organelles responsible for regulating the metabolic status of skeletal muscle. These organelles exhibit remarkable plasticity by adapting their volume, structure, and function in response to chronic exercise, disuse, aging, and disease. A single bout of exercise initiates signaling to provoke increases in mitochondrial biogenesis, balanced by the onset of organelle turnover carried out by the mitophagy pathway. Read More

Annu Rev Physiol 2018 02;80:413-429

Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA; email:

AAA+ proteolytic machines use energy from ATP hydrolysis to degrade damaged, misfolded, or unneeded proteins. Protein degradation occurs within a barrel-shaped self-compartmentalized peptidase. Before protein substrates can enter this peptidase, they must be unfolded and then translocated through the axial pore of an AAA+ ring hexamer. Read More