Metabolism
- Splicing factor ESRP1 controls ER‐positive breast cancer by altering metabolic pathways
- Yesim Gökmen‐Polar (ypolar{at}iu.edu)*,1,
- Yaseswini Neelamraju2,
- Chirayu P Goswami3,
- Yuan Gu1,
- Xiaoping Gu1,
- Gouthami Nallamothu1,
- Edyta Vieth1,
- Sarath C Janga4,5,6,
- Michael Ryan7,8 and
- Sunil S Badve (sbadve{at}iupui.edu)*,1,9,10
- 1Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, IN, USA
- 2Department of Biochemistry and Molecular Genetics, University of Virginia, Charlottesville, VA, USA
- 3Department of Bioinformatics, Thomas Jefferson University Hospitals, Philadelphia, PA, USA
- 4Department of BioHealth Informatics, School of Informatics and Computing, IUPUI, Indianapolis, IN, USA
- 5Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN, USA
- 6Centre for Computational Biology and Bioinformatics Indiana University School of Medicine, Indianapolis, IN, USA
- 7Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
- 8In Silico Solutions, Falls Church, VA, USA
- 9Indiana University Melvin and Bren Simon Cancer Center, Indianapolis, IN, USA
- 10Department of Medicine, Indiana University School of Medicine, Indianapolis, IN, USA
- ↵*
Corresponding author. Tel: +1 317 274 3609; E‐mail: ypolar{at}iu.edu
Corresponding author. Tel: +1 317 278 9335; E‐mail: sbadve{at}iupui.edu
RNA binding protein ESRP1 is known to regulate EMT by modifying alternative splicing events. In ER‐positive breast cancer ESRP1 modulates growth without triggering EMT, and acts as a novel regulator of metabolic pathways.
Synopsis
RNA binding protein ESRP1 is known to regulate EMT by modifying alternative splicing events. In ER‐positive breast cancer ESRP1 modulates growth without triggering EMT, and acts as a novel regulator of metabolic pathways.
ESRP1 is a marker of poor prognosis in ER‐positive but not in ER‐negative breast cancer.
Depletion of ESRP1 in ER+ breast cancer models reduces tumor growth.
ESRP1 regulates the EMT splicing signature in ER+ cells, but this is not associated with EMT.
ESRP1 alters the levels of FASN, SCD1 and PHGDH both at mRNA and protein levels.
EMBO Reports (2019) 20: e46078
- Received March 7, 2018.
- Revision received December 4, 2018.
- Accepted December 11, 2018.
- © 2019 The Authors
- Peroxisome biogenesis, membrane contact sites, and quality control
- Jean‐Claude Farré1,
- Shanmuga S Mahalingam1,
- Marco Proietto1 and
- Suresh Subramani (ssubramani{at}ucsd.edu)*,1
- 1Section of Molecular Biology, Division of Biological Sciences, University of California, San Diego, CA, USA
- ↵*Corresponding author. Tel: +1 858 534 2327; E‐mail: ssubramani{at}ucsd.edu
Peroxisomes have important roles in cellular metabolism, human health, redox homeostasis, intracellular metabolite transfer and signalling. This comprehensive review discusses how peroxisomes are generated, how they communicate with other organelles and how quality control mechanisms operate to maintain their homeostasis.
EMBO Reports (2019) 20: e46864
- Received August 4, 2018.
- Revision received October 8, 2018.
- Accepted November 16, 2018.
- © 2018 The Authors
- Arginine methylation of SIRT7 couples glucose sensing with mitochondria biogenesis
- Wei‐Wei Yan1,
- Yun‐Liu Liang1,
- Qi‐Xiang Zhang2,
- Di Wang1,
- Ming‐Zhu Lei2,
- Jia Qu1,
- Xiang‐Huo He3,
- Qun‐Ying Lei1,4 and
- Yi‐Ping Wang (yiping_wang{at}fudan.edu.cn)*,1
- 1Fudan University Shanghai Cancer Center, Cancer Metabolism Laboratory, Institutes of Biomedical Sciences, Shanghai Medical College, Fudan University, Shanghai, China
- 2Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, Shanghai, China
- 3Fudan University Shanghai Cancer Center, Institutes of Biomedical Sciences, Shanghai Medical College, Fudan University, Shanghai, China
- 4State Key Laboratory of Medical Neurobiology, Fudan University, Shanghai, China
- ↵*Corresponding author. Tel: +86 21 54237902; E‐mail: yiping_wang{at}fudan.edu.cn
PRMT6 methylates and thereby inhibits SIRT7, which epigenetically promotes mitochondria biogenesis and connects it to glucose availability in an AMPK‐dependent manner.
Synopsis
PRMT6 methylates and thereby inhibits SIRT7, which epigenetically promotes mitochondria biogenesis and connects it to glucose availability in an AMPK‐dependent manner.
PRMT6 methylates SIRT7 at R388 to suppress its H3K18 deacetylase activity.
PRMT6 modulates SIRT7 methylation in an AMPK‐dependent manner.
SIRT7 methylation connects glucose sensing with mitochondria biogenesis.
EMBO Reports (2018) 19: e46377
- Received May 7, 2018.
- Revision received September 6, 2018.
- Accepted October 12, 2018.
- © 2018 The Authors
- Regulator of Calcineurin 1 helps coordinate whole‐body metabolism and thermogenesis
- David Rotter1,†,
- Heshan Peiris2,†,
- D Bennett Grinsfelder1,
- Alyce M Martin2,
- Jana Burchfield1,
- Valentina Parra3,
- Christi Hull1,
- Cyndi R Morales1,
- Claire F Jessup4,
- Dusan Matusica4,
- Brian W Parks5,
- Aldons J Lusis6,
- Ngoc Uyen Nhi Nguyen1,
- Misook Oh1,7,
- Israel Iyoke1,
- Tanvi Jakkampudi1,
- D Randy McMillan1,8,
- Hesham A Sadek1,
- Matthew J Watt9,
- Rana K Gupta10,
- Melanie A Pritchard11,
- Damien J Keating (damien.keating{at}flinders.edu.au)*,2,12 and
- Beverly A Rothermel (beverly.rothermel{at}utsouthwestern.edu)*,1,13
- 1Division of Cardiology, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX, USA
- 2Department of Human Physiology and Centre for Neuroscience, Flinders University, Adelaide, SA, Australia
- 3Faculty of Chemical and Pharmaceutical Sciences & Faculty of Medicine, Advanced Center for Chronic Diseases (ACCDiS) and Center for Exercise Metabolism and Cancer (CEMC), University of Chile, Santiago, Chile
- 4Department of Anatomy and Histology and Centre for Neuroscience, Flinders University, Adelaide, SA, Australia
- 5Department of Nutritional Sciences, University of Wisconsin‐Madison, Madison, WI, USA
- 6Division of Cardiology, Department of Medicine, University of California at Los Angeles, Los Angeles, CA, USA
- 7Department of Chemistry, Pohang University of Science and Technology, Pohang, South Korea
- 8Children's Medical Centre, Dallas, TX, USA
- 9The Department of Physiology and Monash Biomedicine Discovery Institute, Metabolic Disease and Obesity Program, Monash University, Clayton, Vic., Australia
- 10Touchstone Diabetes Center and Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX, USA
- 11Department of Biochemistry and Molecular Biology, Monash University, Melbourne, Vic., Australia
- 12South Australian Health and Medical Research Institute (SAHMRI), Adelaide, SA, Australia
- 13Department of Molecular Biology, University of Texas Southwestern Medical Centre, Dallas, TX, USA
- ↵*
Corresponding author. Tel: +61 8 82044282; Fax: +61 8 82045768; E‐mail: damien.keating{at}flinders.edu.au
Corresponding author. Tel: +1 2146487428; Fax: +1 2146481450; E‐mail: beverly.rothermel{at}utsouthwestern.edu
↵† These authors contributed equally to this work
Regulator of Calcineurin1 (RCAN1) suppresses two different mechanisms of non‐shivering thermogenesis: the activation of UCP1 expression in white adipose tissue, and sarcolipin expression in skeletal muscle.
Synopsis
Regulator of Calcineurin1 (RCAN1) suppresses two different mechanisms of non‐shivering thermogenesis: the activation of UCP1 expression in white adipose tissue, and sarcolipin expression in skeletal muscle.
Mice deficient for Rcan1 have an elevated metabolic rate and are resistant to diet‐induced obesity.
Tissue‐specific gene expression profiles from inbred mouse strains demonstrate a high correlation between Rcan1 expression in adipose and metabolic syndrome.
The RCAN1 gene is located on chromosome 21 in humans. These findings may provide insights into the challenges of weight regulation in individuals with Down syndrome.
EMBO Reports (2018) 19: e44706
- Received June 26, 2017.
- Revision received September 12, 2018.
- Accepted October 5, 2018.
- © 2018 The Authors
- Brown adipocyte glucose metabolism: a heated subject
- Mohammed K Hankir (hankir_m{at}klinik.uni-wuerzburg.de)*,1,2 and
- Martin Klingenspor (mk{at}tum.de)*,3,4
- 1Department of Experimental Surgery, University Hospital Wuerzburg, Wuerzburg, Germany
- 2German Research Foundation Collaborative Research Center in Obesity Mechanisms 1052, University of Leipzig, Leipzig, Germany
- 3Chair of Molecular Nutritional Medicine, TUM School of Life Sciences Weihenstephan, Technical University of Munich, Freising, Germany
- 4EKFZ ‐ Else Kröner‐Fresenius Center for Nutritional Medicine, Technical University of Munich, Freising, Germany
- ↵*
Corresponding author. Tel: +49 9312 01 31728; E‐mail: hankir_m{at}klinik.uni-wuerzburg.de
Corresponding author. Tel: +49 8161 71 2386; E‐mail: mk{at}tum.de
Recent data provide insight into how activated brown adipocytes handle glucose. This review discusses contributions of intracellular glycolysis, lactate production, lipogenesis, lipolysis, and beta‐oxidation to BAT thermogenesis and whole‐body thermal, energy and glucose balance.
EMBO Reports (2018) 19: e46404
- Received May 9, 2018.
- Revision received June 22, 2018.
- Accepted July 20, 2018.
- © 2018 The Authors
- A novel regulator of autophagosome biogenesis and lipid droplet dynamics
Autophagosome biogenesis is the key event associated with the stress‐responsive autophagic pathway, allowing the capture of specific cargoes and their delivery to the lysosomal degradative compartment. Although the endoplasmatic reticulum (ER) appears to be central for the assembly of autophagosomal membranes, it is also involved in several events regulating trafficking and local signaling, e.g., the establishment of contact sites with other organelles, the vesicular transport to the Golgi apparatus, and the biogenesis and turnover of lipid droplets. In this issue of EMBO reports, Moretti et al [1] identify the ER transmembrane protein TMEM41B as a novel regulator of autophagosome biogenesis and unravel its involvement in lipid droplet dynamics, also highlighting the role of ER components at the interface of lipid metabolism and regulation of autophagy.
See also: F Moretti et al (September 2018)
Autophagosome biogenesis is a key event associated with stress‐responsive pathways. A study in this issue identifies the ER transmembrane protein TMEM41B as novel regulator of autophagosome biogenesis, lipid droplet homeostasis and mitochondrial respiration.
EMBO Reports (2018) 19: e46858
- © 2018 The Authors
- TMEM41B is a novel regulator of autophagy and lipid mobilization
- Francesca Moretti1,
- Phil Bergman2,
- Stacie Dodgson3,
- David Marcellin1,
- Isabelle Claerr1,
- Jonathan M Goodwin2,5,
- Rowena DeJesus2,
- Zhao Kang2,
- Christophe Antczak2,
- Damien Begue1,
- Debora Bonenfant1,
- Alexandra Graff4,
- Christel Genoud4,
- John S Reece‐Hoyes2,
- Carsten Russ2,
- Zinger Yang2,
- Gregory R Hoffman2,
- Matthias Mueller1,
- Leon O Murphy2,5,
- Ramnik J Xavier3 and
- Beat Nyfeler (beat.nyfeler{at}novartis.com)*,1
- 1Novartis Institutes for BioMedical Research, Basel, Switzerland
- 2Novartis Institutes for BioMedical Research, Cambridge, MA, USA
- 3Harvard Medical School, Massachusetts General Hospital, Boston, MA, USA
- 4Friedrich Miescher Institute for Biomedical Research, Basel, Switzerland
- 5Present Address: Casma Therapeutics, Cambridge, MA, USA
- ↵*Corresponding author. Tel: +41 792612693; E‐mail: beat.nyfeler{at}novartis.com
Autophagy maintains cellular homeostasis by targeting damaged organelles, pathogens or misfolded proteins for lysosomal degradation. The ER transmembrane protein TMEM41B is a novel regulator of autophagosome biogenesis, lipid droplet homeostasis and mitochondrial respiration.
Synopsis
Autophagy maintains cellular homeostasis by targeting damaged organelles, pathogens or misfolded proteins for lysosomal degradation. The ER transmembrane protein TMEM41B is a novel regulator of autophagosome biogenesis, lipid droplet homeostasis and mitochondrial respiration.
TMEM41B localizes to the endoplasmic reticulum.
Knockout of TMEM41B impairs autophagosome biogenesis and lysosomal delivery of cargo.
Absence of TMEM41B results in enlarged lipid droplets.
TMEM41B is required for mobilization and mitochondrial β‐oxidation of fatty acids.
EMBO Reports (2018) 19: e45889
- Received February 1, 2018.
- Revision received July 3, 2018.
- Accepted July 12, 2018.
- © 2018 Novartis Institute for Biomedical Research
- Mitochondrial hyperfusion causes neuropathy in a fly model of CMT2A
Charcot‐Marie‐Tooth neuropathy type 2A is thought to be caused by impaired mitochondrial fusion. A study in this issue now establishes a fly model to show that mainly increased mitochondrial fusion drives CMT2A.
EMBO Reports (2018) 19: e46502
- © 2018 The Authors
- Mitofusin gain and loss of function drive pathogenesis in Drosophila models of CMT2A neuropathy
- Najla El Fissi1,
- Manuel Rojo2,
- Aїcha Aouane1,
- Esra Karatas2,
- Gabriela Poliacikova1,
- Claudine David2,
- Julien Royet1 and
- Thomas Rival (thomas.rival{at}univ-amu.fr)*,1
- 1Aix Marseille University, CNRS, IBDM, Marseille, France
- 2University of Bordeaux, CNRS, Institut de Biochimie et Génétique Cellulaires (IBGC), UMR 5095, Bordeaux, France
- ↵*Corresponding author. Tel: +33 491 26 92 42; Fax: +33 491 69 89 77; E‐mail: thomas.rival{at}univ-amu.fr
In vivo expression in Drosophila motor neurons reveals that the two most prevalent forms of mitofusin alleles associated with CMT2A neuropathy (R94Q and R364W) have opposite effects on mitochondrial fusion.
Synopsis
In vivo expression in Drosophila motor neurons reveals that the two most prevalent forms of mitofusin alleles associated with CMT2A neuropathy (R94Q and R364W) have opposite effects on mitochondrial fusion.
Mutations near/within the GTP‐binding domain of mitofusin (R94Q and T105M) inhibit fusion and trigger aggregation.
Mutations within Helix‐Bundle 1 (R364W and L76P) enhance mitochondrial fusion.
Aggregation and excess fusion both impact on mitochondrial distribution and turn over and induce locomotor defects in Drosophila.
EMBO Reports (2018) 19: e45241
- Received September 26, 2017.
- Revision received May 16, 2018.
- Accepted May 23, 2018.
- © 2018 The Authors
- Mitochondrial adaptation in obesity is a ClpPicated business
Quality control systems that maintain mitochondrial oxidative phosphorylation (OXPHOS) include rescue by mitochondrial fusion, elimination of dysfunctional mitochondria by mitophagy, and degradation of damaged proteins by proteases. ClpP is an ATP‐dependent protease located in the mitochondrial matrix and mutated in Perrault syndrome, causing gonadal atrophy and hearing loss. Given that hearing loss is common in mitochondrial diseases caused by mtDNA mutations, ClpP was proposed to be part of the quality control system to maintain proper mitochondrial OXPHOS function. Two recent studies independently report that deletion of ClpP in mice protects from insulin resistance and obesity by increasing mitochondrial OXPHOS capacity and browning in gonadal white adipose tissue and mitochondrial coupling in brown adipose tissue [1], [2]. Furthermore, liver‐ and muscle‐specific deletion of ClpP has no major effects on insulin resistance. These studies reveal that ClpP might be involved in tissue‐specific mitochondrial remodeling in response to metabolic demands, rather than exclusively removing damaged proteins to maintain OXPHOS capacity.
See also: Becker et al (May 2018) and Bhaskaran et al (March 2018)
Two recent studies independently show that loss of the mitochondrial protease ClpP protects mice from insulin resistance and diet‐induced obesity.
EMBO Reports (2018) 19: e46295
- © 2018 The Authors
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