Authors

Stuart Smith, 1 Children’s Hospital Oakland Research Institute, Oakland, California
Andrej Witkowski, 1 Children’s Hospital Oakland Research Institute, Oakland, California
Ayesha Moghul, 1 Children’s Hospital Oakland Research Institute, Oakland, California
Yuko Yoshinaga, 1 Children’s Hospital Oakland Research Institute, Oakland, California
Michael Nefedov, 1 Children’s Hospital Oakland Research Institute, Oakland, California
Pieter de Jong, 1 Children’s Hospital Oakland Research Institute, Oakland, California
Dejiang Fong, 2 Department of Medicine, University of California Los Angeles, Los Angeles, California
Yiping Tu, 2 Department of Medicine, University of California Los Angeles, Los Angeles, California
Han Yu, 2 Department of Medicine, University of California Los Angeles, Los Angeles, California
Stephen G. Young, 2 Department of Medicine, University of California Los Angeles, Los Angeles, California
Thomas Pham, Children’s Hospital Oakland Research Institute, Oakland, California
Carling Cheung, Children’s Hospital Oakland Research Institute, Oakland, California
Shana M. Katzman, 4 School of Veterinary Medicine, University of California Davis, Davis, California
Martin D. Brand, Buck Institute for Research on Aging, Novato, California
Casey L. Quinlan, Buck Institute for Research on Aging, Novato, California
Marcel Fens, Children’s Hospital Oakland Research Institute, Oakland, California
Frans Kuypers, Children’s Hospital Oakland Research Institute, Oakland, California
Stephanie Misquitta, Children’s Hospital Oakland Research Institute, Oakland, California
Stephen M. Griffey, Children’s Hospital Oakland Research Institute, Oakland, California
Son Tran, Children’s Hospital Oakland Research Institute, Oakland, California
Afshin Gharib, Dominican University of California, San Rafael, CaliforniaFollow
Jens Knudsen, 6 Department of Biochemistry and Molecular Biology, Odense University, Odense, Denmark
Hans Kristian Hannibal-Bach, 6 Department of Biochemistry and Molecular Biology, Odense University, Odense, Denmark
Grace Wang, Children’s Hospital Oakland Research Institute, Oakland, California
Sandra Larkin, Children’s Hospital Oakland Research Institute, Oakland, California
Jennifer Thweatt, Children’s Hospital Oakland Research Institute, Oakland, California
Saloni Pasta, Children’s Hospital Oakland Research Institute, Oakland, California

Document Type

Article

Source

PLoS ONE

ISSN

1932-6203

Volume

7

Issue

10

First Page

e47196

Publication Date

10-2012

Department

Psychology

Abstract

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

Rights

Copyright © 2012 The Author(s)

PubMed ID

23077570

Creative Commons License

Creative Commons Attribution 3.0 License
This work is licensed under a Creative Commons Attribution 3.0 License.

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