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Volume 6, Issue 10, pp. 454 - 493, October 2019

Issue cover
Cover: Aerial view of Grand Prismatic Spring; Hot Springs, Midway & Lower Geyser Basin, Yellowstone National Park. The spring is approximately 250 by 300 feet (75 by 91 m) in size. This photo shows steam rising from hot and sterile deep azure blue water (owing to the light absorbing overtone of an OH stretch which is shifted to 698 nm by hydrogen bonding) in the center surrounded by huge mats of brilliant orange algae, bacteria and archaea. The color is due to the ratio of chlorophyll to carotenoid molecules produced by the organisms. During summertime the chlorophyll content of the organisms is low and thus the mats appear orange, red, or yellow. However during the winter, the mats are usually dark green, because sunlight is more scarce and the microbes produce more chlorophyll to compensate, thereby masking the carotenoid colors (imgae by Jim Peaco, National Park Service (USA); retrieved via Wikimedia Commons; the image was modified by MIC). The cover is published under the Creative Commons Attribution (CC BY) license. Enlarge issue cover

Reviews

Gut microbial metabolites in depression: understanding the biochemical mechanisms

Giorgia Caspani, Sidney Kennedy, Jane A. Foster and Jonathan Swann

page 454-481 | 10.15698/mic2019.10.693 | Full text | PDF | Abstract

Gastrointestinal and central function are intrinsically connected by the gut microbiota, an ecosystem that has co-evolved with the host to expand its biotransformational capabilities and interact with host physiological processes by means of its metabolic products. Abnormalities in this microbiota-gut-brain axis have emerged as a key component in the pathophysiology of depression, leading to more research attempting to understand the neuroactive potential of the products of gut microbial metabolism. This review explores the potential for the gut microbiota to contribute to depression and focuses on the role that microbially-derived molecules – neurotransmitters, short-chain fatty acids, indoles, bile acids, choline metabolites, lactate and vitamins – play in the context of emotional behavior. The future of gut-brain axis research lies is moving away from association, towards the mechanisms underlying the relationship between the gut bacteria and depressive behavior. We propose that direct and indirect mechanisms exist through which gut microbial metabolites affect depressive behavior: these include (i) direct stimulation of central receptors, (ii) peripheral stimulation of neural, endocrine, and immune mediators, and (iii) epigenetic regulation of histone acetylation and DNA methylation. Elucidating these mechanisms is essential to expand our understanding of the etiology of depression, and to develop new strategies to harness the beneficial psychotropic effects of these molecules. Overall, the review highlights the potential for dietary interventions to represent such novel therapeutic strategies for major depressive disorder.

Research Reports

Proline metabolism regulates replicative lifespan in the yeast Saccharomyces cerevisiae

Yukio Mukai, Yuka Kamei, Xu Liu, Shan Jiang, Yukiko Sugimoto, Noreen Suliani binti Mat Nanyan, Daisuke Watanabe and Hiroshi Takagi

page 482-490 | 10.15698/mic2019.10.694 | Full text | PDF | Abstract

In many plants and microorganisms, intracellular proline has a protective role against various stresses, including heat-shock, oxidation and osmolarity. Environmental stresses induce cellular senescence in a variety of eukaryotes. Here we showed that intracellular proline regulates the replicative lifespan in the budding yeast Saccharomyces cerevisiae. Deletion of the proline oxidase gene PUT1 and expression of the γ-glutamate kinase mutant gene PRO1-I150T that is less sensitive to feedback inhibition accumulated proline and extended the replicative lifespan of yeast cells. Inversely, disruption of the proline biosynthetic genes PRO1, PRO2, and CAR2 decreased stationary proline level and shortened the lifespan of yeast cells. Quadruple disruption of the proline transporter genes unexpectedly did not change intracellular proline levels and replicative lifespan. Overexpression of the stress-responsive transcription activator gene MSN2 reduced intracellular proline levels by inducing the expression of PUT1, resulting in a short lifespan. Thus, the intracellular proline levels at stationary phase was positively correlated with the replicative lifespan. Furthermore, multivariate analysis of amino acids in yeast mutants deficient in proline metabolism showed characteristic metabolic profiles coincident with longevity: acidic and basic amino acids and branched-chain amino acids positively contributed to the replicative lifespan. These results allude to proline metabolism having a physiological role in maintaining the lifespan of yeast cells.

Microreviews

Inhibiting eukaryotic ribosome biogenesis: Mining new tools for basic research and medical applications

Lisa Kofler, Michael Prattes and Helmut Bergler

page 491-493 | 10.15698/mic2019.10.695 | Full text | PDF | Abstract

The formation of new ribosomes is a fundamental cellular process for each living cell and is tightly interwoven with cell cycle control and proliferation. Minimal disturbances of this pathway can result in ribosomopathies including an increased risk for certain cancer types. Thus, targeting ribosome biogenesis is an emerging strategy in cancer therapy. However, due to its complex nature, we are only at the beginning to understand the dynamics of the ribosome biogenesis pathway. One arising approach that will help us to embrace the tight timely cascade of events that is needed to form a new ribosome is the use of targeted chemical inhibition. However, only very few specific chemical inhibitors of the ribosome biogenesis pathway have been identified so far. Here we review our recently published screen to identify novel inhibitors of the ribosome biogenesis pathway in yeast (Awad et al., 2019, BMC Biology). These inhibitors can provide novel tools for basic research and can serve as starting-points to develop new chemotherapeutics.

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