[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"detail-sidebar-cat-0-en-105":3,"doc-seo-201719-105":59,"doc-detail-201719-en":130},{"code":4,"msg":5,"data":6},0,"success",[7,13,18,23,28,33,38,43,48,51,55],{"id":8,"doc_module":4,"doc_module_name":9,"category_name":10,"show_sort_weight":11,"slug":12},1,"Document","Story & Novel",90,"story-novel",{"id":14,"doc_module":4,"doc_module_name":9,"category_name":15,"show_sort_weight":16,"slug":17},2,"Literature",80,"literature",{"id":19,"doc_module":4,"doc_module_name":9,"category_name":20,"show_sort_weight":21,"slug":22},4,"Exam",70,"exam",{"id":24,"doc_module":4,"doc_module_name":9,"category_name":25,"show_sort_weight":26,"slug":27},5,"Comic",60,"comic",{"id":29,"doc_module":4,"doc_module_name":9,"category_name":30,"show_sort_weight":31,"slug":32},6,"Technology",50,"technology",{"id":34,"doc_module":4,"doc_module_name":9,"category_name":35,"show_sort_weight":36,"slug":37},7,"Healthcare",40,"healthcare",{"id":39,"doc_module":4,"doc_module_name":9,"category_name":40,"show_sort_weight":41,"slug":42},8,"Research & Report",30,"research-report",{"id":44,"doc_module":4,"doc_module_name":9,"category_name":45,"show_sort_weight":46,"slug":47},9,"Religion & Spirituality",20,"religion-spirituality",{"id":46,"doc_module":4,"doc_module_name":9,"category_name":49,"show_sort_weight":46,"slug":50},"World Cup","world-cup",{"id":52,"doc_module":4,"doc_module_name":9,"category_name":53,"show_sort_weight":52,"slug":54},10,"Lifestyle","lifestyle",{"id":56,"doc_module":4,"doc_module_name":9,"category_name":57,"show_sort_weight":24,"slug":58},19,"General","general",{"code":4,"msg":60,"data":61},"ok",{"site_id":62,"language":63,"slug":64,"title":65,"keywords":66,"description":67,"schema_data":68,"social_meta":123,"head_meta":125,"extra_data":127,"updated_unix":129},105,"en","compromised-mitochondrial-fatty-acid-synthesis-in-transgenic-mice-results-in-defective-protein-lipoylation-and-energy-disequilibrium","Compromised Mitochondrial Fatty Acid Synthesis in Transgenic Mice Results in Defective Protein Lipoylation and Energy Disequilibrium","","A mouse model with compromised mitochondrial fatty acid synthesis was engineered to define how this pathway shapes mitochondrial performance and whole-body health. Tamoxifen-inducible Cre-lox strategies reduced expression of mitochondrial malonyl CoA-acyl carrier protein transacylase (Mcat), with variable effects across tissues. Despite increased food intake, affected mice showed poor weight gain, reduced activity, white adipose loss, muscle weakness, kyphosis, alopecia, hypothermia, and reduced lifespan. Mcat deficiency likely stems from diminished octanoyl precursor production for lipoylation of key dehydrogenase complexes, impairing citric acid cycle activity and energy homeostasis. Exogenous free lipoate rescue was limited to liver and did not restore normal energy metabolism.",{"@graph":69,"@context":122},[70,84,105],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":35,"@type":76,"position":81},"https://docshare.wps.com/document/healthcare/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/compromised-mitochondrial-fatty-acid-synthesis-in-transgenic-mice-results-in-defective-protein-lipoylation-and-energy-disequilibrium/201719/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/compromised-mitochondrial-fatty-acid-synthesis-in-transgenic-mice-results-in-defective-protein-lipoylation-and-energy-disequilibrium/201719.png","ImageObject",300,407,{"name":92,"@type":93},"Margaret","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-09-19","2026-09-04",true,{"@type":102,"interactionType":103,"userInteractionCount":14},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"What genetic change was used to compromise mitochondrial fatty acid synthesis in the transgenic mice?","Question",{"text":112,"@type":113},"The study reduced mitochondrial malonyl CoA-acyl carrier protein transacylase (Mcat) expression using a tamoxifen-inducible Cre-lox system targeting the nuclear Mcat gene.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"What phenotypes were observed in Mcat-deficient mice?",{"text":117,"@type":113},"Compared with controls, affected mice consumed more food but failed to gain weight, were less physically active, lost white adipose tissue, had reduced muscle strength, kyphosis and alopecia, developed hypothermia, and had shortened lifespan.",{"name":119,"@type":110,"acceptedAnswer":120},"How does the paper explain the link between Mcat loss and disrupted energy metabolism?",{"text":121,"@type":113},"The phenotype is attributed to reduced synthesis, in multiple tissues, of octanoyl precursors required for posttranslational lipoylation of pyruvate and α-ketoglutarate dehydrogenase complexes, leading to impaired citric acid cycle capacity and disrupted energy metabolism.","https://schema.org",{"og:url":83,"og:type":124,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":126,"canonical":83},"index,follow",{"doc_id":128,"site_id":62},201719,1788537636,{"code":4,"msg":5,"data":131},{"doc_id":128,"user_id":132,"nickname":92,"user_avatar":133,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":14,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":139,"language":140,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":141,"faqs":142,"seo_title":143,"seo_description":67,"update_tm":129,"read_time":36},137451207643,"https://ap-avatar.wpscdn.com/davatar_3d24733baf745e90a7e4bdd5f77d97b2","UCLA  \nUCLA Previously Published Works  \nTitle  \nCompromised Mitochondrial Fatty Acid Synthesis in Transgenic Mice Results in Defective Protein Lipoylation and Energy Disequilibrium  \nPermalink  \n[https://escholarship.org/uc/item/6c01d78z](https://escholarship.org/uc/item/6c01d78z)  \nJournal  \nPLOS ONE, 7(10)  \nISSN  \n1932-6203  \nAuthors  \nSmith, Stuart  \nWitkowski, Andrzej Moghul, Ayesha et al.  \nPublication Date  \n2012  \nDOI  \n10.1371/journal.pone.0047196  \nCopyright Information  \nThis work is made available under the terms of a Creative Commons Attribution License, available at [https://creativecommons.org/licenses/by/4.0/](https://creativecommons.org/licenses/by/4.0/)  \nPeer reviewed  \n[eScholarship.org](eScholarship.org) Powered by the California Digital Library  \nUniversity of California  \nCompromised Mitochondrial Fatty Acid Synthesis in Transgenic Mice Results in Defective Protein Lipoylation and Energy Disequilibrium  \nStuart Smith 1*, Andrzej Witkowski 1, Ayesha Moghul 1, Yuko Yoshinaga1, Michael Nefedov 1, Pieter de Jong 1, Dejiang Feng 1, Loren Fong2, Yiping Tu2, Yan Hu2, Stephen G. Young2, Thomas Pham 1, Carling Cheung 1, Shana M. Katzman3, Martin D. Brand3, Casey L. Quinlan3, Marcel Fens 1, Frans Kuypers 1, Stephanie Misquitta1, Stephen M. Griffey4, Son Tran 1, Afshin Gharib 1,5, Jens Knudsen6, Hans Kristian Hannibal-Bach6, Grace Wang 1, Sandra Larkin1, Jennifer Thweatt 1, Saloni Pasta1  \n1 Children’s Hospital Oakland Research Institute, Oakland, California, United States of America, 2 Department of Medicine, University of California Los Angeles, Los Angeles, California, United States of America, 3Buck Institute for Research on Aging, Novato, California, United States of America, 4School of Veterinary Medicine, University of California Davis, Davis, California, United States of America, 5Dominican University of California, San Rafael, California, United States of America, 6Department of Biochemistry and Molecular Biology, Odense University, Odense, Denmark  \n\n| Abstract\u003Cbr>A mouse model with compromised mitochondrial fatty acid synthesis has been engineered in order to assess the role of this pathway in mitochondrial function and overall health. Reduction in the expression of mitochondrial malonyl CoA-acyl carrier protein transacylase, a key enzyme in the pathway encoded by the nuclear Mcat gene, was achieved to varying extents in all examined tissues employing tamoxifen-inducible Cre-lox technology. Although affected mice consumed more food than control animals, they failed to gain weight, were less physically active, suffered from loss of white adipose tissue, reduced muscle strength, kyphosis, alopecia, hypothermia and shortened lifespan. The Mcat-deficient phenotype is attributed primarily to reduced synthesis, in several tissues, of the octanoyl precursors required for the posttranslational lipoylation of pyruvate and a-ketoglutarate dehydrogenase complexes, resulting in diminished capacity of the citric acid cycle and disruption of energy metabolism. The presence of an alternative lipoylation pathway that utilizes exogenous free lipoate appears restricted to liver and alone is insufficient for preservation of normal energy metabolism. Thus, de novo synthesis of precursors for the protein lipoylation pathway plays a vital role in maintenance of mitochondrial function and overall vigor. |\n| --- |\n| Citation: Smith S, Witkowski A, Moghul A, Yoshinaga Y, Nefedov M, et al. (2012) Compromised Mitochondrial Fatty Acid Synthesis in Transgenic Mice Results in\u003Cbr>Defective Protein Lipoylation and Energy Disequilibrium. PLoS ONE 7(10): e47196 . doi:10.1371/journal.pone.0047196\u003Cbr>Editor: Wolf-Hagen Schunck, Max Delbrueck Center for Molecular Medicine, Germany Received July 11, 2012; Accepted September 10, 2012; Published October 15, 2012\u003Cbr>Copyright: 􀀂 2012 Smith et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution,","cbCaifKZoqYYPmH3","https://ap.wps.com/l/cbCaifKZoqYYPmH3","pdf",1183594,16,"English","# Abstract\n# Introduction\n## Mitochondrial diseases and diagnostic challenges\n## Fatty acid synthesis pathways and nuclear-encoded enzymes","[{\"question\":\"What genetic change was used to compromise mitochondrial fatty acid synthesis in the transgenic mice?\",\"answer\":\"The study reduced mitochondrial malonyl CoA-acyl carrier protein transacylase (Mcat) expression using a tamoxifen-inducible Cre-lox system targeting the nuclear Mcat gene.\"},{\"question\":\"What phenotypes were observed in Mcat-deficient mice?\",\"answer\":\"Compared with controls, affected mice consumed more food but failed to gain weight, were less physically active, lost white adipose tissue, had reduced muscle strength, kyphosis and alopecia, developed hypothermia, and had shortened lifespan.\"},{\"question\":\"How does the paper explain the link between Mcat loss and disrupted energy metabolism?\",\"answer\":\"The phenotype is attributed to reduced synthesis, in multiple tissues, of octanoyl precursors required for posttranslational lipoylation of pyruvate and α-ketoglutarate dehydrogenase complexes, leading to impaired citric acid cycle capacity and disrupted energy metabolism.\"}]","Compromised Mitochondrial Fatty Acid Synthesis in Transgenic Mice Results in Defective Protein Lipoylation and Energy Disequilibrium | PDF"]