Mitochondrial H+ Leak and Thermogenesis

2021 ◽  
Vol 84 (1) ◽  
Author(s):  
Ambre M. Bertholet ◽  
Yuriy Kirichok
Keyword(s):  
Metabolic Disorders ◽  
Molecular Mechanisms ◽  
Uncoupling Protein ◽  
Annual Review ◽  
Publication Date ◽  
Uncoupling Protein 1 ◽  
Current Field ◽  
Atp Production ◽  
Metabolic Substrates ◽  
Primary Focus

Mitochondria of all tissues convert various metabolic substrates into two forms of energy: ATP and heat. Historically, the primary focus of research in mitochondrial bioenergetics was on the mechanisms of ATP production, while mitochondrial thermogenesis received significantly less attention. Nevertheless, mitochondrial heat production is crucial for the maintenance of body temperature, regulation of the pace of metabolism, and prevention of oxidative damage to mitochondria and the cell. In addition, mitochondrial thermogenesis has gained significance as a pharmacological target for treating metabolic disorders. Mitochondria produce heat as the result of H+ leak across their inner membrane. This review provides a critical assessment of the current field of mitochondrial H+ leak and thermogenesis, with a focus on the molecular mechanisms involved in the function and regulation of uncoupling protein 1 and the ADP/ATP carrier, the two proteins that mediate mitochondrial H+ leak. Expected final online publication date for the Annual Review of Physiology, Volume 84 is February 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

Molecular Force Measurement with Tension Sensors

2021 ◽  
Vol 50 (1) ◽  
Author(s):  
Lisa S. Fischer ◽  
Srishti Rangarajan ◽  
Tanmay Sadhanasatish ◽  
Carsten Grashoff
Keyword(s):  
Molecular Mechanisms ◽  
Force Measurement ◽  
Annual Review ◽  
Publication Date ◽  
Mechanical Forces ◽  
Biophysical Parameters ◽  
Cellular Mechanotransduction ◽  
Molecular Force ◽  
Molecular Forces ◽  
Physical Principles

The ability of cells to generate mechanical forces, but also to sense, adapt to, and respond to mechanical signals, is crucial for many developmental, postnatal homeostatic, and pathophysiological processes. However, the molecular mechanisms underlying cellular mechanotransduction have remained elusive for many decades, as techniques to visualize and quantify molecular forces across individual proteins in cells were missing. The development of genetically encoded molecular tension sensors now allows the quantification of piconewton-scale forces that act upon distinct molecules in living cells and even whole organisms. In this review, we discuss the physical principles, advantages, and limitations of this increasingly popular method. By highlighting current examples from the literature, we demonstrate how molecular tension sensors can be utilized to obtain access to previously unappreciated biophysical parameters that define the propagation of mechanical forces on molecular scales. We discuss how the methodology can be further developed and provide a perspective on how the technique could be applied to uncover entirely novel aspects of mechanobiology in the future. Expected final online publication date for the Annual Review of Biophysics, Volume 50 is May 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

Systems Biology of the Vasopressin V2 Receptor: New Tools for Discovery of Molecular Actions of a GPCR

2021 ◽  
Vol 62 (1) ◽  
Author(s):  
Lihe Chen ◽  
Hyun Jun Jung ◽  
Arnab Datta ◽  
Euijung Park ◽  
Brian G. Poll ◽  
...  
Keyword(s):  
Systems Biology ◽  
Large Scale ◽  
Molecular Mechanisms ◽  
Water Channel ◽  
Peptide Hormone ◽  
Annual Review ◽  
Publication Date ◽  
Large Scale Data ◽  
V2 Receptor ◽  
Scale Data

Systems biology can be defined as the study of a biological process in which all of the relevant components are investigated together in parallel to discover the mechanism. Although the approach is not new, it has come to the forefront as a result of genome sequencing projects completed in the first few years of the current century. It has elements of large-scale data acquisition (chiefly next-generation sequencing–based methods and protein mass spectrometry) and large-scale data analysis (big data integration and Bayesian modeling). Here we discuss these methodologies and show how they can be applied to understand the downstream effects of GPCR signaling, specifically looking at how the neurohypophyseal peptide hormone vasopressin, working through the V2 receptor and PKA activation, regulates the water channel aquaporin-2. The emerging picture provides a detailed framework for understanding the molecular mechanisms involved in water balance disorders, pointing the way to improved treatment of both polyuric disorders and water-retention disorders causing dilutional hyponatremia. Expected final online publication date for the Annual Review of Pharmacology and Toxicology, Volume 62 is January 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

Molecules from the Microbiome

2021 ◽  
Vol 90 (1) ◽  
Author(s):  
Emilee E. Shine ◽  
Jason M. Crawford
Keyword(s):  
Small Molecules ◽  
Molecular Mechanisms ◽  
System Development ◽  
Human Microbiome ◽  
Host Responses ◽  
Annual Review ◽  
Publication Date ◽  
Mechanistic Studies ◽  
Immune System Development ◽  
Interdisciplinary Approaches

The human microbiome encodes a second genome that dwarfs the genetic capacity of the host. Microbiota-derived small molecules can directly target human cells and their receptors or indirectly modulate host responses through functional interactions with other microbes in their ecological niche. Their biochemical complexity has profound implications for nutrition, immune system development, disease progression, and drug metabolism, as well as the variation in these processes that exists between individuals. While the species composition of the human microbiome has been deeply explored, detailed mechanistic studies linking specific microbial molecules to host phenotypes are still nascent. In this review, we discuss challenges in decoding these interaction networks, which require interdisciplinary approaches that combine chemical biology, microbiology, immunology, genetics, analytical chemistry, bioinformatics, and synthetic biology. We highlight important classes of microbiota-derived small molecules and notable examples. An understanding of these molecular mechanisms is central to realizing the potential of precision microbiome editing in health, disease, and therapeutic responses. Expected final online publication date for the Annual Review of Biochemistry, Volume 90 is June 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

Regulation of Mitochondrial Ca2+ Uptake

2020 ◽  
Vol 83 (1) ◽  
Author(s):  
Elizabeth Murphy ◽  
Charles Steenbergen
Keyword(s):  
Cell Death ◽  
Genetic Alterations ◽  
Annual Review ◽  
Publication Date ◽  
Mitochondrial Matrix ◽  
Atp Production ◽  
The Past ◽  
Specific Manner ◽  
Insight Into ◽  
Disease Specific

Mitochondria are responsible for ATP production but are also known as regulators of cell death, and mitochondrial matrix Ca2+ is a key modulator of both ATP production and cell death. Although mitochondrial Ca2+ uptake and efflux have been studied for over 50 years, it is only in the past decade that the proteins responsible for mitochondrial Ca2+ uptake and efflux have been identified. The identification of the mitochondrial Ca2+ uniporter (MCU) led to an explosion of studies identifying regulators of the MCU. The levels of these regulators vary in a tissue- and disease-specific manner, providing new insight into how mitochondrial Ca2+ is regulated. This review focuses on the proteins responsible for mitochondrial transport and what we have learned from mouse studies with genetic alterations in these proteins. Expected final online publication date for the Annual Review of Physiology, Volume 83 is February 10, 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

scholarly journals Rheb promotes brown fat thermogenesis by Notch-dependent activation of the PKA signaling pathway

2019 ◽  
Vol 11 (9) ◽  
pp. 781-790 ◽  
Author(s):  
Wen Meng ◽  
Xiuci Liang ◽  
Ting Xiao ◽  
Jing Wang ◽  
Jie Wen ◽  
...  
Keyword(s):  
Gene Expression ◽  
High Fat Diet ◽  
Energy Homeostasis ◽  
Molecular Mechanisms ◽  
Uncoupling Protein ◽  
Regulatory Subunit ◽  
Uncoupling Protein 1 ◽  
Brown Adipocytes ◽  
Brown Adipose ◽  
Beige Fat

Abstract Increasing brown and beige fat thermogenesis have an anti-obesity effect and thus great metabolic benefits. However, the molecular mechanisms regulating brown and beige fat thermogenesis remain to be further elucidated. We recently found that fat-specific knockout of Rheb promoted beige fat thermogenesis. In the current study, we show that Rheb has distinct effects on thermogenic gene expression in brown and beige fat. Fat-specific knockout of Rheb decreased protein kinase A (PKA) activity and thermogenic gene expression in brown adipose tissue of high-fat diet-fed mice. On the other hand, overexpression of Rheb activated PKA and increased uncoupling protein 1 expression in brown adipocytes. Mechanistically, Rheb overexpression in brown adipocytes increased Notch expression, leading to disassociation of the regulatory subunit from the catalytic subunit of PKA and subsequent PKA activation. Our study demonstrates that Rheb, by selectively modulating thermogenic gene expression in brown and beige adipose tissues, plays an important role in regulating energy homeostasis.

Adipose Tissue Fibrosis in Obesity: Etiology and Challenges

2021 ◽  
Vol 84 (1) ◽  
Author(s):  
Geneviève Marcelin ◽  
Emmanuel L. Gautier ◽  
Karine Clément
Keyword(s):  
Insulin Resistance ◽  
Adipose Tissue ◽  
Molecular Mechanisms ◽  
Whole Body ◽  
Annual Review ◽  
Publication Date ◽  
Tissue Fibrosis ◽  
Adipose Tissue Remodeling ◽  
Metabolic Dysfunctions ◽  
Body Energy

Obesity is a chronic and progressive process affecting whole-body energy balance and is associated with comorbidities development. In addition to increased fat mass, obesity induces white adipose tissue (WAT) inflammation and fibrosis, leading to local and systemic metabolic dysfunctions, such as insulin resistance (IR). Accordingly, limiting inflammation or fibrosis deposition may improve IR and glucose homeostasis. Although no targeted therapy yet exists to slow or reverse adipose tissue fibrosis, a number of findings have clarified the underlying cellular and molecular mechanisms. In this review, we highlight adipose tissue remodeling events shown to be associated with fibrosis deposition, with a focus on adipose progenitors involved in obesity-induced healthy as well as unhealthy WAT expansion. Expected final online publication date for the Annual Review of Physiology, Volume 84 is February 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

From Physics to Russian Studies and on into China Research: My Meandering Journey Toward Sociology

2021 ◽  
Vol 47 (1) ◽  
Author(s):  
Martin King Whyte
Keyword(s):  
Annual Review ◽  
Chinese Society ◽  
Publication Date ◽  
Growing Up ◽  
Sociological Study ◽  
Social Patterns ◽  
Chinese Studies ◽  
Research Problems ◽  
Primary Focus ◽  
The Cold War

I was initially reluctant to become a sociologist because my father, William Foote Whyte, was a prominent sociologist. Growing up during the Cold War led me in sequence through studying physics to Russian studies and then into Chinese studies, and I finally chose sociology as the best discipline for research on China, the primary focus of my career. The theoretical and methodological eclecticism of our discipline enabled me to do research on many intriguing research problems regarding contemporary Chinese society, first at a distance from Hong Kong and then through a series of collaborative surveys conducted within China. I found I could use sociological theories to more accurately and objectively interpret Chinese social patterns, while at the same time some paradoxical features of Chinese society enabled me to challenge existing social science theories. Over the course of my career I was gratified to see the sociological study of China move from being a somewhat marginal specialty into joining the mainstream of our discipline. Expected final online publication date for the Annual Review of Sociology, Volume 47 is July 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

Receptor-Ribosome Coupling: A Link Between Extrinsic Signals and mRNA Translation in Neuronal Compartments

2022 ◽  
Vol 45 (1) ◽  
Author(s):  
Max Koppers ◽  
Christine E. Holt
Keyword(s):  
Intracellular Signaling ◽  
Messenger Rna ◽  
Molecular Mechanisms ◽  
Synapse Formation ◽  
Cell Communication ◽  
Mrna Translation ◽  
Common Mechanism ◽  
Annual Review ◽  
Publication Date ◽  
Spatiotemporal Resolution

Axons receive extracellular signals that help to guide growth and synapse formation during development and to maintain neuronal function and survival during maturity. These signals relay information via cell surface receptors that can initiate local intracellular signaling at the site of binding, including local messenger RNA (mRNA) translation. Direct coupling of translational machinery to receptors provides an attractive way to activate this local mRNA translation and change the local proteome with high spatiotemporal resolution. Here, we first discuss the increasing evidence that different external stimuli trigger translation of specific subsets of mRNAs in axons via receptors and thus play a prominent role in various processes in both developing and mature neurons. We then discuss the receptor-mediated molecular mechanisms that regulate local mRNA translational with a focus on direct receptor-ribosome coupling. We advance the idea that receptor-ribosome coupling provides several advantages over other translational regulation mechanisms and is a common mechanism in cell communication. Expected final online publication date for the Annual Review of Neuroscience, Volume 45 is July 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

Enteroviruses and Type 1 Diabetes: Multiple Mechanisms and Factors?

2021 ◽  
Vol 73 (1) ◽  
Author(s):  
Richard E. Lloyd ◽  
Manasi Tamhankar ◽  
Åke Lernmark
Keyword(s):  
Type 1 Diabetes ◽  
Molecular Mechanisms ◽  
Subsequent Development ◽  
Annual Review ◽  
Publication Date ◽  
Virus Infections ◽  
Persistent Infections ◽  
Complex Interactions ◽  
Genetic And Environmental Factors

Type 1 diabetes (T1D) is a chronic autoimmune disease characterized by insulin deficiency and resultant hyperglycemia. Complex interactions of genetic and environmental factors trigger the onset of autoimmune mechanisms responsible for development of autoimmunity to β cell antigens and subsequent development of T1D. A potential role of virus infections has long been hypothesized, and growing evidence continues to implicate enteroviruses as the most probable triggering viruses. Recent studies have strengthened the association between enteroviruses and development of autoimmunity in T1D patients, potentially through persistent infections. Enterovirus infections may contribute to different stages of disease development. We review data from both human cohort studies and experimental research exploring the potential roles and molecular mechanisms by which enterovirus infections can impact disease outcome. Expected final online publication date for the Annual Review of Medicine, Volume 73 is January 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

scholarly journals Importance of adipocyte browning in the evolution of endothermy

2020 ◽  
Vol 375 (1793) ◽  
pp. 20190134 ◽  
Author(s):  
Martin Jastroch ◽  
Frank Seebacher
Keyword(s):  
Adipose Tissue ◽  
Heat Production ◽  
Molecular Mechanisms ◽  
Uncoupling Protein ◽  
Muscular Activity ◽  
Evolutionary Significance ◽  
Potential Contribution ◽  
Atp Production ◽  
Evolutionary Innovation ◽  
Brown Adipose

Endothermy changes the relationship between organisms and their environment fundamentally, and it is therefore of major ecological and evolutionary significance. Endothermy is characterized by non-shivering thermogenesis, that is metabolic heat production in the absence of muscular activity. In many eutherian mammals, brown adipose tissue (BAT) is an evolutionary innovation that facilitates non-shivering heat production in mitochondria by uncoupling food-derived substrate oxidation from chemical energy (ATP) production. Consequently, energy turnover is accelerated resulting in increased heat release. The defining characteristics of BAT are high contents of mitochondria and vascularization, and the presence of uncoupling protein 1. Recent insights, however, reveal that a range of stimuli such as exercise, diet and the immune system can cause the browning of white adipocytes, thereby increasing energy expenditure and heat production even in the absence of BAT. Here, we review the molecular mechanisms that cause browning of white adipose tissue, and their potential contribution to thermoregulation. The significance for palaeophysiology lies in the presence of adipose tissue and the mechanisms that cause its browning and uncoupling in all amniotes. Hence, adipocytes may have played a role in the evolution of endothermy beyond the more specific evolution of BAT in eutherians. This article is part of the theme issue ‘Vertebrate palaeophysiology’.

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