Vamsi K. Mootha

Bio: Vamsi K. Mootha is an academic researcher from Broad Institute. The author has contributed to research in topics: Mitochondrion & Mitochondrial DNA. The author has an hindex of 85, co-authored 227 publications receiving 73860 citations. Previous affiliations of Vamsi K. Mootha include Harvard University & Beth Israel Deaconess Medical Center.

Evolutionary mitochondrial biology in titisee

Abstract: In the spring of 2017, we had the privilege of organizing and chairing the 115th International Titisee Conference (ITC). Since 1962, these invitation-only conferences, sponsored by the Boehringer Ingelheim Fonds, have been held at Lake Titisee, in the Black Forest of southern Germany (https://www.bifonds.de/ titisee-conferences/about-itcs.html). The ITCs have explored a wide variety of themes, typically with the goal of bringing together researchers from different disciplines who might not normally have an opportunity to meet together. The presentation, in an intimate setting, of cutting-edge research by both senior and more junior scientists is aimed at stimulating discussion that will lead to new concepts and new approaches, as well as forging new collaborations. The theme of the 115th ITC was Evolutionary mitochondrial biology: molecular, biochemical, and metabolic diversity (https:// www.bifonds.de/titisee-conferences/past-conferences/past-conference/ items/id-115th-evolutionary-mitochondrial-biology-molecularbiochemical-and-metabolic-diversity.html). The conference featured investigators studying mitochondria from a phylogenetically broad range of eukaryotes, with the goal of exploring the mechanistic basis and physiological consequences of their diversity. The evident enthusiasm of participants and success of the conference encouraged us to suggest a special issue of IUBMB Life that would focus on the theme of the 115th ITC and capture some of the work and ideas discussed. Senior investigators presenting at the conference were invited to submit Critical Reviews or original Research Communications, all peerreviewed, based on their ITC presentation. We are gratified by the response, and present herein a sampling of the work discussed at or emanating from the 115th ITC. As the cover illustration emphasizes, mitochondria come in a wide variety of “flavors,” from conventional aerobic organelles, through anaerobic mitochondria using terminal electron acceptors other than oxygen, to mitochondrion-related organelles (MROs) that dispense with part or all of the mitochondrial genome, the “missing” portions including genes that encode key parts of the system that generates ATP through coupled electron transport/oxidative phosphorylation (OXPHOS). Depending on the degree of reduction in mitochondrial function, particular MROs may generate ATP via substrate-level phosphorylation (as in the hydrogenosome, the first such MRO to be discovered), or they may have completely lost the ability to form ATP (e.g., mitosome). A recent review by Roger et al. (1) provides a comprehensive treatment of the mitochondrion in its various functional and evolutionary forms. Mitochondria were already present in the last eukaryotic common ancestor (2) and, over 1–2 billion years, have undergone tremendous lineage-specific evolution, today exhibiting remarkable molecular, biochemical, and metabolic diversity. While animal mitochondria contain a high-copy circular genome, the mitochondrial genomes of other eukaryotes display a wide array of physical forms, gene arrangements and modes of expression (3). Mitochondria can exhibit variant configurations of the respiratory chain, branching with alternative electron donors or acceptors, all designed to preserve bioenergetics, redox balance, and promote survival under diverse environmental conditions. Examples of this diversity in its various forms appear throughout this special issue. The origin of mitochondria has been the subject of intense interest and spirited debate ever since Lynn Margulis revived the moribund endosymbiont hypothesis in the late 1960s (4). The discovery of DNA in mitochondria and the characterization and comparison of the genes encoded in that genome not only solidified the view that the mitochondrial genome is of bacterial origin, but also pointed clearly to a specific lineage, α-Proteobacteria, as the closest extant relatives of mitochondria (5). Although an α-proteobacterial origin of mitochondria is widely accepted, a complicating factor is that only a small percentage of the mitochondrial proteome (the set of proteins making up the functional mitochondrion) clearly traces to Abbreviations: ITC, International Titisee Conference; mtDNA, mitochondrial DNA; MRO, mitochondrion-related organelle; OXPHOS, oxidative phosphorylation; LECA, last eukaryotic common ancestor; MC, mitochondrial carrier; APC, ATP-Mg/Pi carrier; LEA, late embryogenesis abundant © 2018 International Union of Biochemistry and Molecular Biology Volume 70, Number 12, December 2018, Pages 1184–1187 Address correspondence to: Michael W. Gray, Department of Biochemistry & Molecular Biology and Centre for Comparative Genomics and Evolutionary Bioinformatics, Dalhousie University, Halifax, NS B3H 4R2, Canada. Tel: 1-902-494-2521. Fax: 1-902-494-1355. E-mail: m.w.gray@dal.ca Received 21 September 2018; Accepted 23 September 2018 DOI 10.1002/iub.1958 Published online 24 October 2018 in Wiley Online Library (wileyonlinelibrary.com)

A genetically encoded system for oxygen generation in living cells

Abstract: Significance Oxygen is one of the most important molecules in living systems, playing a key role in energy metabolism, cellular signaling, and disease. At present, we have few if any ways to manipulate molecular oxygen in living cells with high spatiotemporal control. Here, we introduce a genetic strategy for generating oxygen inside human cells, by simultaneously expressing a transporter and a bacterial enzyme. Together, these proteins promote the uptake of chlorite into the cell and enzymatically produce oxygen. We call this genetic technology SupplemeNtal Oxygen Released from ChLorite (SNORCL). This technology will allow investigation of the effects of short, local pulses of oxygen in cells and tissues. Optimized versions of the technology could have direct medical applications.

Procédés et compositions pour traiter des troubles métaboliques

Abstract: La presente invention porte sur des procedes de traitement de troubles caracterises par une activite mitochondriale defectueuse. En particulier, les composes de la presente invention peuvent etre utilises dans le traitement de maladies metaboliques et de maladies neurodegeneratives. Les procedes sont egalement utiles pour augmenter la phosphorylation oxydative ou pour diminuer la production d'espece oxygene reactive (ROS) chez un sujet en ayant besoin.

Gene set enrichment analysis: A knowledge-based approach for interpreting genome-wide expression profiles

Abstract: Although genomewide RNA expression analysis has become a routine tool in biomedical research, extracting biological insight from such information remains a major challenge. Here, we describe a powerful analytical method called Gene Set Enrichment Analysis (GSEA) for interpreting gene expression data. The method derives its power by focusing on gene sets, that is, groups of genes that share common biological function, chromosomal location, or regulation. We demonstrate how GSEA yields insights into several cancer-related data sets, including leukemia and lung cancer. Notably, where single-gene analysis finds little similarity between two independent studies of patient survival in lung cancer, GSEA reveals many biological pathways in common. The GSEA method is embodied in a freely available software package, together with an initial database of 1,325 biologically defined gene sets.

Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources.

Abstract: DAVID bioinformatics resources consists of an integrated biological knowledgebase and analytic tools aimed at systematically extracting biological meaning from large gene/protein lists. This protocol explains how to use DAVID, a high-throughput and integrated data-mining environment, to analyze gene lists derived from high-throughput genomic experiments. The procedure first requires uploading a gene list containing any number of common gene identifiers followed by analysis using one or more text and pathway-mining tools such as gene functional classification, functional annotation chart or clustering and functional annotation table. By following this protocol, investigators are able to gain an in-depth understanding of the biological themes in lists of genes that are enriched in genome-scale studies.

limma powers differential expression analyses for RNA-sequencing and microarray studies

Abstract: limma is an R/Bioconductor software package that provides an integrated solution for analysing data from gene expression experiments. It contains rich features for handling complex experimental designs and for information borrowing to overcome the problem of small sample sizes. Over the past decade, limma has been a popular choice for gene discovery through differential expression analyses of microarray and high-throughput PCR data. The package contains particularly strong facilities for reading, normalizing and exploring such data. Recently, the capabilities of limma have been significantly expanded in two important directions. First, the package can now perform both differential expression and differential splicing analyses of RNA sequencing (RNA-seq) data. All the downstream analysis tools previously restricted to microarray data are now available for RNA-seq as well. These capabilities allow users to analyse both RNA-seq and microarray data with very similar pipelines. Second, the package is now able to go past the traditional gene-wise expression analyses in a variety of ways, analysing expression profiles in terms of co-regulated sets of genes or in terms of higher-order expression signatures. This provides enhanced possibilities for biological interpretation of gene expression differences. This article reviews the philosophy and design of the limma package, summarizing both new and historical features, with an emphasis on recent enhancements and features that have not been previously described.

疟原虫var基因转换速率变化导致抗原变异[英]／Paul H, Robert P, Christodoulou Z, et al//Proc Natl Acad Sci U S A

Abstract: 抗原变异可使得多种致病微生物易于逃避宿主免疫应答。表达在感染红细胞表面的恶性疟原虫红细胞表面蛋白1（PfPMP1）与感染红细胞、内皮细胞、树突状细胞以及胎盘的单个或多个受体作用，在黏附及免疫逃避中起关键的作用。每个单倍体基因组var基因家族编码约60种成员，通过启动转录不同的var基因变异体为抗原变异提供了分子基础。