Metabolism
- Glutamine‐utilizing transaminases are a metabolic vulnerability of TAZ/YAP‐activated cancer cells
- Chih‐Sheng Yang1,†,
- Eleni Stampouloglou1,†,
- Nathan M Kingston1,†,
- Liye Zhang2,3,
- Stefano Monti2 and
- Xaralabos Varelas (xvarelas{at}bu.edu)*,1
- 1Department of Biochemistry, Boston University School of Medicine, Boston, MA, USA
- 2Section of Computational Biomedicine, Department of Medicine, Boston University School of Medicine, Boston, MA, USA
- 3Present Address: School of Life Science and Technology, ShanghaiTech University, Shanghai, China
- ↵*Corresponding author. Tel: +1 617 358 4575; E‐mail: xvarelas{at}bu.edu
↵† These authors contributed equally to this work
Elevated levels of the transcriptional regulators TAZ/YAP, key effectors of Hippo pathway signalling, mediate breast cancer cell growth dependence on exogenous glutamine. Cancer cells with high TAZ/YAP activity are sensitive to transaminase inhibition.
Synopsis
Elevated levels of the transcriptional regulators TAZ/YAP, key effectors of Hippo pathway signalling, mediate breast cancer cell growth dependence on exogenous glutamine. Cancer cells with high TAZ/YAP activity are sensitive to transaminase inhibition.
High TAZ/YAP levels alter cellular energetics to promote breast cancer cell growth dependence on exogenous glutamine.
TAZ/YAP promote the expression of glutamic–oxaloacetic transaminase (GOT1) and phosphoserine aminotransferase (PSAT1).
Transaminase inhibition represses breast cancer cell growth in a TAZ/YAP dependent manner.
EMBO Reports (2018) e43577
- Received October 26, 2016.
- Revision received March 19, 2018.
- Accepted March 23, 2018.
- © 2018 The Authors
- Mitochondria and the dynamic control of stem cell homeostasis
- Pawel Lisowski1,2,3,
- Preethi Kannan1,
- Barbara Mlody1 and
- Alessandro Prigione (alessandro.prigione{at}mdc-berlin.de)*,1
- 1Max Delbrueck Center for Molecular Medicine (MDC), Berlin, Germany
- 2Institute of Genetics and Animal Breeding, Polish Academy of Sciences, Magdalenka, Poland
- 3Centre for Preclinical Research and Technology (CePT), Warsaw Medical University, Warsaw, Poland
- ↵*Corresponding author. Tel: +49 30 9406 2871; Fax: +49 30 9406 3696; E‐mail: alessandro.prigione{at}mdc-berlin.de
Dissecting the roles of mitochondria in stem cell homeostasis and differentiation is essential to understand stem cell dynamics and fate. This review discusses how mitochondria are implicated in the acquisition, maintenance and loss of stemness.
EMBO Reports (2018) e45432
- Received November 3, 2017.
- Revision received December 22, 2017.
- Accepted March 21, 2018.
- © 2018 The Authors
- Ticking time bomb? High time for chronobiological research
- 1Institute and Policlinic for Occupational Medicine, Environmental Medicine and Prevention Research, University Hospital of Cologne, Cologne, Germany
- 2Nuffield Department of Clinical Neurosciences, Sleep and Circadian Neuroscience Institute, OMPI G, Sir William Dunn School of Pathology, University of Oxford, Oxford, UK
The 2017 Nobel prize for elucidating the mechanisms of chronobiology highlights the urgent need to better understand our internal clockwork and its effects on health and disease.
- © 2018 The Authors
- CLPP deficiency protects against metabolic syndrome but hinders adaptive thermogenesis
- Christina Becker1,
- Alexandra Kukat1,
- Karolina Szczepanowska1,
- Steffen Hermans1,
- Katharina Senft1,
- Christoph Paul Brandscheid1,
- Priyanka Maiti1 and
- Aleksandra Trifunovic (aleksandra.trifunovic{at}uk-koeln.de)*,1,2
- 1Cologne Excellence Cluster on Cellular Stress Responses in Aging‐Associated Diseases (CECAD) and Institute for Mitochondrial Diseases and Aging, Medical Faculty, University of Cologne, Cologne, Germany
- 2Center for Molecular Medicine (CMMC), University of Cologne, Cologne, Germany
- ↵*Corresponding author. Tel: +49 221 478 84291; E‐mail: aleksandra.trifunovic{at}uk-koeln.de
Complete loss of mitochondrial CLPP protease protects mice from diet‐induced obesity and insulin‐resistance but impairs cold‐induced thermogenesis due to a decline in brown adipocyte function.
Synopsis
Complete loss of mitochondrial CLPP protease makes mice leaner with increased ability for glucose handling and protects them from diet‐induced obesity. In the same time, CLPP ablation also leads to a decline in brown adipocytes function leaving mice unable to cope with a cold‐induced stress due to dysfunctional thermogenesis.
Loss of CLPP protects against HFD‐induced obesity and insulin resistance.
CLPP deficiency increases FAO in white adipose tissue.
Loss of CLPP impairs cold‐induced thermogenesis.
EMBO Reports (2018) e45126
- Received September 5, 2017.
- Revision received February 26, 2018.
- Accepted February 27, 2018.
- © 2018 The Authors
- From white to beige: a new hypothalamic pathway
Understanding how brown and beige adipocytes can be differentially controlled and activated by neuronal circuits is a fundamental prerequisite to fully comprehend the metabolic role that fat tissue plays in energy homeostasis. In this issue of EMBO reports, Wang et al [1] identify a new hypothalamic route that drives the exclusive recruitment of beige fat via the selective control of sympathetic nervous system (SNS) outflow to subcutaneous white adipose tissue. Since the data strongly suggest that the APPL2–AMPK signaling axis is crucial for this activation, this finding sheds a new light on the cross talk between peripheral homeostatic signals and neurons that are part of hypothalamic energy homeostasis regulatory pathways in the ventromedial hypothalamus (VHM) proposing a new defending mechanism to cold and obesity.
See also: B Wang et al (April 2018)
A study in this issue shows that the adaptor protein APPL2 induces activation of RIP‐Cre neurons in the VMH, which enhances sympathetic outflow to sWAT, sWAT beiging and cold tolerance.
EMBO Reports (2018) 19: e45928
- © 2018 The Authors
- Zc3h10 is a novel mitochondrial regulator
- Matteo Audano1,
- Silvia Pedretti1,
- Gaia Cermenati1,
- Elisabetta Brioschi1,
- Giuseppe Riccardo Diaferia2,
- Serena Ghisletti3,
- Alessandro Cuomo2,
- Tiziana Bonaldi2,
- Franco Salerno4,
- Marina Mora4,
- Liliana Grigore5,6,
- Katia Garlaschelli6,
- Andrea Baragetti1,6,
- Fabrizia Bonacina1,
- Alberico Luigi Catapano1,5,
- Giuseppe Danilo Norata1,6,7,
- Maurizio Crestani1,
- Donatella Caruso1,
- Enrique Saez8,
- Emma De Fabiani (emma.defabiani{at}unimi.it)*,1 and
- Nico Mitro (nico.mitro{at}unimi.it)*,1
- 1DiSFeB, Dipartimento di Scienze Farmacologiche e Biomolecolari, Università degli Studi di Milano, Milan, Italy
- 2Department of Experimental Oncology, European Institute of Oncology (IEO), Milan, Italy
- 3Humanitas Clinical and Research Center, Rozzano‐Milan, Italy
- 4Neuromuscular Diseases and Neuroimmunology Unit, Foundation IRCCS C. Besta Neurological Institute, Milan, Italy
- 5IRCSS Multimedica, Milan, Italy
- 6SISA Centre, Bassini Hospital, Cinisello Balsamo, Italy
- 7School of Biomedical Sciences, Curtin Health Innovation Research Institute, Faculty of Health Science, Curtin University, Perth, WA, Australia
- 8Department of Molecular Medicine, The Scripps Research Institute, La Jolla, CA, USA
- ↵*
Corresponding author. Tel: +39 02 50318323; E‐mail: emma.defabiani{at}unimi.it
Corresponding author. Tel: +39 02 50318253; E‐mail: nico.mitro{at}unimi.it
Genome‐wide functional screens coupled to integrated omic approaches identify Zinc finger CCCH‐type containing 10 (Zc3h10) as a new regulator of mitochondrial biology. Zc3h10 silencing in vitro and mutation in vivo are associated with impaired mitochondrial function.
Synopsis
Genome‐wide functional screens coupled to integrated omic approaches identify Zinc finger CCCH‐type containing 10 (Zc3h10) as a new regulator of mitochondrial biology. Zc3h10 silencing in vitro and mutation in vivo are associated with impaired mitochondrial function.
Genomic screens identify the poorly characterized Zc3h10 as a novel mitochondrial regulator.
Zc3h10 silencing in vitro impairs mitochondrial oxidative capacity in myoblasts and delays myogenesis.
Cys105 mutation leads to Zc3h10 loss of function and is associated with compromised metabolic trait and mitochondrial dysfunction in human isolated PBMCs.
EMBO Reports (2018) 19: e45531
- Received November 22, 2017.
- Revision received February 2, 2018.
- Accepted February 7, 2018.
- © 2018 The Authors
- Oncoprotein CIP2A promotes the disassembly of primary cilia and inhibits glycolytic metabolism
- Ae Lee Jeong1,2,
- Hye In Ka1,
- Sora Han1,
- Sunyi Lee1,3,
- Eun‐Woo Lee4,
- Su Jung Soh1,
- Hyun Jeong Joo1,
- Buyanravjkh Sumiyasuren1,
- Ji Young Park1,
- Jong‐Seok Lim1,
- Jong Hoon Park1,
- Myung Sok Lee1 and
- Young Yang (yyang{at}sookmyung.ac.kr)*,1
- 1Division of Biological Sciences, Department of Life Systems, Research Center for Women's Disease, Sookmyung Women's University, Seoul, Korea
- 2New Drug Development Center, Osong Medical Innovation Foundation, Osong, Korea
- 3Drug Evaluation Group, R&D Center CJ HealthCare, Icheon, Korea
- 4Metabolic Regulation Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon, Korea
- ↵*Corresponding author. Tel: +82‐2‐710‐9590; Fax: +82‐2‐2077‐7322; E‐mail: yyang{at}sookmyung.ac.kr
Cancerous inhibitor of protein phosphatase 2A (CIP2A) is located at the cilia transition zone and inhibits cilia assembly and the glycolytic pathway. CIP2A depletion increases ciliated cells and cilia length and enhances the glycolytic pathway.
Synopsis
Cancerous inhibitor of protein phosphatase 2A (CIP2A) is located at the cilia transition zone and inhibits cilia assembly and the glycolytic pathway. CIP2A depletion increases ciliated cells and cilia length and enhances the glycolytic pathway.
CIP2A depletion‐induced glycolytic activation is not dependent on cilia assembly.
Enhanced cilia assembly activates glycolytic metabolism regardless of CIP2A.
EMBO Reports (2018) e45144
- Received September 11, 2017.
- Revision received February 5, 2018.
- Accepted February 8, 2018.
- © 2018 The Authors
- Activation of hypothalamic RIP‐Cre neurons promotes beiging of WAT via sympathetic nervous system
- Baile Wang1,2,
- Ang Li3,
- Xiaomu Li4,
- Philip WL Ho2,
- Donghai Wu5,
- Xiaoqi Wang6,
- Zhuohao Liu1,2,
- Kelvin KL Wu7,
- Sonata SY Yau8,
- Aimin Xu (amxu{at}hku.hk)*,1,2,9 and
- Kenneth KY Cheng (kenneth.ky.cheng{at}polyu.edu.hk)*,7
- 1State Key Laboratory of Pharmaceutical Biotechnology, The University of Hong Kong, Hong Kong, China
- 2Department of Medicine, The University of Hong Kong, Hong Kong, China
- 3Guangdong‐Hong Kong‐Macau Institute of CNS Regeneration, Joint International Research Laboratory of CNS Regeneration Ministry of Education, Guangdong Medical Key Laboratory of Brain Function and Diseases, Jinan University, Guangzhou, China
- 4Department of Endocrinology and Metabolism, Zhongshan Hospital, Fudan University, Shanghai, China
- 5Key Laboratory of Regenerative Biology and Guangdong Provincial, Key Laboratory of Stem Cell and Regenerative Medicine, Guangzhou Institute of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China
- 6Department of Surgery, The University of Hong Kong, Hong Kong, China
- 7Department of Health Technology and Informatics, The Hong Kong Polytechnic University, Hong Kong, China
- 8Department of Rehabilitation Science, The Hong Kong Polytechnic University, Hong Kong, China
- 9Department of Pharmacology & Pharmacy, The University of Hong Kong, Hong Kong, China
- ↵*
Corresponding author. Tel: +852 3917 9754; E‐mail: amxu{at}hku.hk
Corresponding author. Tel: +852 3400 8912; E‐mail: kenneth.ky.cheng{at}polyu.edu.hk
The adaptor protein APPL2 induces activation of RIP‐Cre neurons in the VMH, which enhances sympathetic outflow to sWAT, sWAT beiging and cold tolerance.
Synopsis
The adaptor protein APPL2 induces activation of RIP‐Cre neurons in the VMH, which enhances sympathetic outflow to sWAT, sWAT beiging and cold tolerance.
Ablation of APPL2 in RIP‐Cre neurons in the VMH suppresses beiging in sWAT without influencing BAT metabolism, leading to cold intolerance and increased adiposity.
APPL2 activates VMH RIP‐Cre neurons through AMPK inhibition.
Pharmacogenetic activation of RIP‐Cre neurons induces beiging and increases energy expenditure in mice.
EMBO Reports (2018) 19: e44977
- Received August 8, 2017.
- Revision received January 23, 2018.
- Accepted January 25, 2018.
- © 2018 The Authors
- SORCS1 and SORCS3 control energy balance and orexigenic peptide production
- Aygul Subkhangulova (Aygul.Subkhangulova{at}mdc-berlin.de)*,1,
- Anna R Malik1,
- Guido Hermey2,
- Oliver Popp1,
- Gunnar Dittmar1,3,5,
- Thomas Rathjen1,
- Matthew N Poy1,
- Alexander Stumpf4,
- Prateep Sanker Beed4,
- Dietmar Schmitz4,
- Tilman Breiderhoff1 and
- Thomas E Willnow (willnow{at}mdc-berlin.de)*,1,3
- 1Max‐Delbrueck‐Center for Molecular Medicine, Berlin, Germany
- 2Institute for Molecular and Cellular Cognition, Center for Molecular Neurobiology, University Medical Center Hamburg‐Eppendorf, Hamburg, Germany
- 3Berlin Institute of Health, Berlin, Germany
- 4Neuroscience Research Center, Charité – University Medicine, Berlin, Germany
- 5Present Address: Department of Oncology, Luxembourg Institute of Health, Strassen, Luxembourg
- ↵*
Corresponding author. Tel: +49 30 9406 3749; E‐mail: Aygul.Subkhangulova{at}mdc-berlin.de
Corresponding author. Tel: +49 30 9406 2569; E‐mail: willnow{at}mdc-berlin.de
Diabetes‐associated sorting receptors SORCS1 and SORCS3 play a role in central control of metabolism. In mice, loss of the proteins increases production of orexigenic agouti‐related peptide, possibly via enhancement of neurotrophin signaling in AgRP neurons.
Synopsis
Diabetes‐associated sorting receptors SORCS1 and SORCS3 play a role in central control of metabolism. In mice, loss of the proteins increases production of orexigenic agouti‐related peptide, possibly via enhancement of neurotrophin signaling in AgRP neurons.
Combined deficiency for SORCS1 and SORCS3 results in a state of chronic energy excess that coincides with elevated expression of Agrp and its transcriptional activator KLF4 in AgRP neurons of the hypothalamus.
SORCS1 and SORCS3 inhibit signaling by brain‐derived neurotrophic factor (BDNF) via reducing the surface pool of the BDNF receptor TrkB.
Loss of SORCS1 and SORCS3 enhances neuronal sensitivity to BDNF, possibly explaining the increased levels of the BDNF‐responsive gene product KLF4, and its target Agrp, in hypothalamic neurons of mutant mice.
EMBO Reports (2018) 19: e44810
- Received July 12, 2017.
- Revision received January 15, 2018.
- Accepted January 22, 2018.
- © 2018 The Authors. Published under the terms of the CC BY 4.0 license
This is an open access article under the terms of the Creative Commons Attribution 4.0 License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
- Loss of mitochondrial protease ClpP protects mice from diet‐induced obesity and insulin resistance
- Shylesh Bhaskaran1,
- Gavin Pharaoh1,2,
- Rojina Ranjit1,
- Ashley Murphy1,
- Satoshi Matsuzaki1,
- Binoj C Nair3,
- Brittany Forbes1,
- Suzana Gispert4,
- Georg Auburger4,
- Kenneth M Humphries1,
- Michael Kinter1,
- Timothy M Griffin1 and
- Sathyaseelan S Deepa (deepa-sathyaseelan{at}ouhsc.edu)*,1,5
- 1Aging and Metabolism Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK, USA
- 2Department of Physiology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA
- 3The University of Texas MD Anderson Cancer Center, Houston, TX, USA
- 4Experimental Neurology, Goethe University Medical School, Frankfurt am Main, Germany
- 5Present Address: Department of Geriatric Medicine and the Reynolds Oklahoma Center on Aging, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA
- ↵*Corresponding author. Tel: +1 405 271 2633; E‐mail: deepa-sathyaseelan{at}ouhsc.edu
Mitochondrial matrix protease ClpP is proposed to play an important role in the initiation of mammalian mitochondrial unfolded protein response (UPRmt). This study reveals that ClpP deficiency in mice has paradoxical beneficial effects on metabolism and ClpP might be dispensable for mammalian UPRmt initiation.
Synopsis
Mitochondrial matrix protease ClpP is proposed to play an important role in the initiation of mammalian mitochondrial unfolded protein response (UPRmt). This study reveals that ClpP deficiency in mice has paradoxical beneficial effects on metabolism and ClpP might be dispensable for mammalian UPRmt initiation.
ClpP−/− mice have reduced adiposity and improved insulin sensitivity.
Mitochondrial biogenesis markers and respiration are selectively up‐regulated in white adipose tissue of ClpP−/− mice.
ClpP−/− mice are protected from diet‐induced obesity, glucose intolerance, and insulin resistance.
EMBO Reports (2018) 19: e45009
- Received August 14, 2017.
- Revision received December 8, 2017.
- Accepted December 22, 2017.
- © 2018 The Authors
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