Genomes and Genes
- Jha P, McDevitt M, Gupta R, Quirós P, Williams E, Gariani K, et al. Systems Analyses Reveal Physiological Roles and Genetic Regulators of Liver Lipid Species. Cell Syst. 2018;6:722-733.e6 pubmed publisher..This work provides a foundation and resource for understanding the genetic regulation and physiological significance of lipid species. ..
- Moullan N, Mouchiroud L, Wang X, Ryu D, Williams E, Mottis A, et al. Tetracyclines Disturb Mitochondrial Function across Eukaryotic Models: A Call for Caution in Biomedical Research. Cell Rep. 2015;10:1681-1691 pubmed publisher..Furthermore, these results caution against extensive use of tetracyclines in livestock due to potential downstream impacts on the environment and human health. ..
- Williams E, Auwerx J. The Convergence of Systems and Reductionist Approaches in Complex Trait Analysis. Cell. 2015;162:23-32 pubmed publisher..Together, these strategies are beginning to drive the next era in complex trait research, paving the way to improve agriculture and toward more personalized medicine. ..
- Jha P, McDevitt M, Halilbasic E, Williams E, Quirós P, Gariani K, et al. Genetic Regulation of Plasma Lipid Species and Their Association with Metabolic Phenotypes. Cell Syst. 2018;6:709-721.e6 pubmed publisher..This work provides a resource to identify plausible genes regulating the measured lipid species and their association with metabolic traits. ..
- Zhang H, Menzies K, Auwerx J. The role of mitochondria in stem cell fate and aging. Development. 2018;145: pubmed publisher..This Review will also highlight some recent progress in mitochondrial therapeutics that may present attractive strategies for improving stem cell function as a basis for regenerative medicine and healthy aging. ..
- Teperino R, Schoonjans K, Auwerx J. Histone methyl transferases and demethylases; can they link metabolism and transcription?. Cell Metab. 2010;12:321-327 pubmed publisher..Despite the preliminary evidence that methyltranferases and demethylases could link metabolic signals to chromatin and alter transcription, further research is indispensable to consolidate these enticing observations. ..
- CantÃ³ C, Menzies K, Auwerx J. NAD(+) Metabolism and the Control of Energy Homeostasis: A Balancing Act between Mitochondria and the Nucleus. Cell Metab. 2015;22:31-53 pubmed publisher..In this review, we summarize how NAD(+) metabolism links energy status with adaptive cellular and organismal responses and how this knowledge can be therapeutically exploited. ..
- Greggio C, Jha P, Kulkarni S, Lagarrigue S, Broskey N, Boutant M, et al. Enhanced Respiratory Chain Supercomplex Formation in Response to Exercise in Human Skeletal Muscle. Cell Metab. 2017;25:301-311 pubmed publisher..Taken together, our results provide the first evidence that exercise affects the stoichiometry of supercomplex formation in humans and thus reveal a novel adaptive mechanism for increased energy demand. ..
- Gariani K, Ryu D, Menzies K, Yi H, Stein S, Zhang H, et al. Inhibiting poly ADP-ribosylation increases fatty acid oxidation and protects against fatty liver disease. J Hepatol. 2017;66:132-141 pubmed publisher..PARP inhibitors given as a treatment in two different mouse models of NAFLD confer a protection against its development. PARP inhibitors may therefore represent a novel and practical pharmacological approach for treating NAFLD. ..
- Matilainen O, QuirÃ³s P, Auwerx J. Mitochondria and Epigenetics - Crosstalk in Homeostasis and Stress. Trends Cell Biol. 2017;27:453-463 pubmed publisher..Finally, we describe the essential role of some histone modifications in regulating the mitochondrial unfolded protein response (UPRmt) and the mitochondrial stress-dependent lifespan extension. ..
- QuirÃ³s P, Prado M, Zamboni N, D Amico D, Williams R, Finley D, et al. Multi-omics analysis identifies ATF4 as a key regulator of the mitochondrial stress response in mammals. J Cell Biol. 2017;216:2027-2045 pubmed publisher..Our data illustrate the value of a multiomics approach to characterize complex cellular networks and provide a versatile resource to identify new regulators of mitochondrial-related diseases. ..
- D Amico D, Sorrentino V, Auwerx J. Cytosolic Proteostasis Networks of the Mitochondrial Stress Response. Trends Biochem Sci. 2017;42:712-725 pubmed publisher..This mitochondria to cytosol network extends the current model of the mitochondrial stress response, with potential applications in the treatment of mitochondrial disease. ..
- Katsyuba E, Auwerx J. Modulating NAD+ metabolism, from bench to bedside. EMBO J. 2017;36:2670-2683 pubmed publisher..Here, we review the fundamental aspects of NAD+ biochemistry and metabolism and discuss how boosting NAD+ content can help ameliorate mitochondrial homeostasis and as such improve healthspan and lifespan. ..
- Matilainen O, Sleiman M, Quirós P, Garcia S, Auwerx J. The chromatin remodeling factor ISW-1 integrates organismal responses against nuclear and mitochondrial stress. Nat Commun. 2017;8:1818 pubmed publisher..HSF-1 and ISW-1 hence emerge as a central mediator of this multi-compartment proteostatic response regulating longevity. ..
- Ryu D, Jo Y, Lo Sasso G, Stein S, Zhang H, Perino A, et al. A SIRT7-dependent acetylation switch of GABPÎ²1 controls mitochondrial function. Cell Metab. 2014;20:856-69 pubmed publisher..Altogether, these data suggest that SIRT7 is a dynamic nuclear regulator of mitochondrial function through its impact on GABPÎ²1 function. ..
- Bai P, Canto C, Oudart H, Brunyánszki A, Cen Y, Thomas C, et al. PARP-1 inhibition increases mitochondrial metabolism through SIRT1 activation. Cell Metab. 2011;13:461-468 pubmed publisher..These data show how PARP-1 inhibition has strong metabolic implications through the modulation of SIRT1 activity, a property that could be useful in the management not only of metabolic diseases, but also of cancer. ..
- Wang X, Auwerx J. Systems Phytohormone Responses to Mitochondrial Proteotoxic Stress. Mol Cell. 2017;68:540-551.e5 pubmed publisher..Our data ascertain that mitochondrial protein quality control pathways, such as the UPRmt, are conserved in plants and that hormone signaling is an essential mediator that regulates mitochondrial proteostasis...
- Pirinen E, Canto C, Jo Y, Morató L, Zhang H, Menzies K, et al. Pharmacological Inhibition of poly(ADP-ribose) polymerases improves fitness and mitochondrial function in skeletal muscle. Cell Metab. 2014;19:1034-41 pubmed publisher..elegans. Overall, our work validates in worm, mouse, and human models that PARP inhibition may be used to treat both genetic and acquired muscle dysfunction linked to defective mitochondrial function. ..
- Merkwirth C, Jovaisaite V, Durieux J, Matilainen O, Jordan S, Quirós P, et al. Two Conserved Histone Demethylases Regulate Mitochondrial Stress-Induced Longevity. Cell. 2016;165:1209-1223 pubmed publisher..These findings illustrate an evolutionary conserved epigenetic mechanism that determines the rate of aging downstream of mitochondrial perturbations. ..
- Wu Y, Williams E, Dubuis S, Mottis A, Jovaisaite V, Houten S, et al. Multilayered genetic and omics dissection of mitochondrial activity in a mouse reference population. Cell. 2014;158:1415-1430 pubmed publisher..elegans, mice, and humans. Overall, these examples demonstrate the value of an integrated multilayered omics approach to characterize complex metabolic phenotypes. ..