Myc stimulates nuclearly encoded mitochondrial genes and mitochondrial biogenesis

Feng Li, Yunyue Wang, Karen I. Zeller, James J. Potter, Diane R. Wonsey, Kathryn A. O'Donnell, Jung Whan Kim, Jason T. Yustein, Linda A. Lee, Chi V. Dang

Research output: Contribution to journalArticle

340 Citations (Scopus)

Abstract

Although several genes involved in mitochondrial function are direct Myc targets, the role of Myc in mitochondrial biogenesis has not been directly established. We determined the effects of ectopic Myc expression or the loss of Myc on mitochondrial biogenesis. Induction of Myc in P493-6 cells resulted in increased oxygen consumption and mitochondrial mass and function. Conversely, compared to wild-type Myc fibroblasts, Myc null rat fibroblasts have diminished mitochondrial mass and decreased number of normal mitochondria. Reconstitution of Myc expression in Myc null fibroblasts partially restored mitochondrial mass and function and normal-appearing mitochondria. Concordantly, we also observed in primary hepatocytes that acute deletion of floxed murine Myc by Cre recombinase resulted in diminished mitochondrial mass in primary hepatocytes. Our microarray analysis of genes responsive to Myc in human P493-6 B lymphocytes supports a role for Myc in mitochondrial biogenesis, since genes involved in mitochondrial structure and function are overrepresented among the Myc-induced genes. In addition to the known direct binding of Myc to many genes involved in mitochondrial structure and function, we found that Myc binds the TFAM gene, which encodes a key transcriptional regulator and mitochondrial DNA replication factor, both in P493-6 lymphocytes with high ectopic MYC expression and in serum-stimulated primary human 2091 fibroblasts with induced endogenous MYC. These observations support a pivotal role for Myc in regulating mitochondrial biogenesis.

Original languageEnglish (US)
Pages (from-to)6225-6234
Number of pages10
JournalMolecular and Cellular Biology
Volume25
Issue number14
DOIs
StatePublished - Jul 2005

Fingerprint

Mitochondrial Genes
Organelle Biogenesis
Fibroblasts
Genes
Hepatocytes
Mitochondria
myc Genes
Microarray Analysis
DNA Replication
Mitochondrial DNA
Oxygen Consumption
B-Lymphocytes
Lymphocytes
Serum

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cell Biology

Cite this

Myc stimulates nuclearly encoded mitochondrial genes and mitochondrial biogenesis. / Li, Feng; Wang, Yunyue; Zeller, Karen I.; Potter, James J.; Wonsey, Diane R.; O'Donnell, Kathryn A.; Kim, Jung Whan; Yustein, Jason T.; Lee, Linda A.; Dang, Chi V.

In: Molecular and Cellular Biology, Vol. 25, No. 14, 07.2005, p. 6225-6234.

Research output: Contribution to journalArticle

Li, F, Wang, Y, Zeller, KI, Potter, JJ, Wonsey, DR, O'Donnell, KA, Kim, JW, Yustein, JT, Lee, LA & Dang, CV 2005, 'Myc stimulates nuclearly encoded mitochondrial genes and mitochondrial biogenesis', Molecular and Cellular Biology, vol. 25, no. 14, pp. 6225-6234. https://doi.org/10.1128/MCB.25.14.6225-6234.2005
Li, Feng ; Wang, Yunyue ; Zeller, Karen I. ; Potter, James J. ; Wonsey, Diane R. ; O'Donnell, Kathryn A. ; Kim, Jung Whan ; Yustein, Jason T. ; Lee, Linda A. ; Dang, Chi V. / Myc stimulates nuclearly encoded mitochondrial genes and mitochondrial biogenesis. In: Molecular and Cellular Biology. 2005 ; Vol. 25, No. 14. pp. 6225-6234.
@article{86cd82f58d6448b6a762b8884cfbaabf,
title = "Myc stimulates nuclearly encoded mitochondrial genes and mitochondrial biogenesis",
abstract = "Although several genes involved in mitochondrial function are direct Myc targets, the role of Myc in mitochondrial biogenesis has not been directly established. We determined the effects of ectopic Myc expression or the loss of Myc on mitochondrial biogenesis. Induction of Myc in P493-6 cells resulted in increased oxygen consumption and mitochondrial mass and function. Conversely, compared to wild-type Myc fibroblasts, Myc null rat fibroblasts have diminished mitochondrial mass and decreased number of normal mitochondria. Reconstitution of Myc expression in Myc null fibroblasts partially restored mitochondrial mass and function and normal-appearing mitochondria. Concordantly, we also observed in primary hepatocytes that acute deletion of floxed murine Myc by Cre recombinase resulted in diminished mitochondrial mass in primary hepatocytes. Our microarray analysis of genes responsive to Myc in human P493-6 B lymphocytes supports a role for Myc in mitochondrial biogenesis, since genes involved in mitochondrial structure and function are overrepresented among the Myc-induced genes. In addition to the known direct binding of Myc to many genes involved in mitochondrial structure and function, we found that Myc binds the TFAM gene, which encodes a key transcriptional regulator and mitochondrial DNA replication factor, both in P493-6 lymphocytes with high ectopic MYC expression and in serum-stimulated primary human 2091 fibroblasts with induced endogenous MYC. These observations support a pivotal role for Myc in regulating mitochondrial biogenesis.",
author = "Feng Li and Yunyue Wang and Zeller, {Karen I.} and Potter, {James J.} and Wonsey, {Diane R.} and O'Donnell, {Kathryn A.} and Kim, {Jung Whan} and Yustein, {Jason T.} and Lee, {Linda A.} and Dang, {Chi V.}",
year = "2005",
month = "7",
doi = "10.1128/MCB.25.14.6225-6234.2005",
language = "English (US)",
volume = "25",
pages = "6225--6234",
journal = "Molecular and Cellular Biology",
issn = "0270-7306",
publisher = "American Society for Microbiology",
number = "14",

}

TY - JOUR

T1 - Myc stimulates nuclearly encoded mitochondrial genes and mitochondrial biogenesis

AU - Li, Feng

AU - Wang, Yunyue

AU - Zeller, Karen I.

AU - Potter, James J.

AU - Wonsey, Diane R.

AU - O'Donnell, Kathryn A.

AU - Kim, Jung Whan

AU - Yustein, Jason T.

AU - Lee, Linda A.

AU - Dang, Chi V.

PY - 2005/7

Y1 - 2005/7

N2 - Although several genes involved in mitochondrial function are direct Myc targets, the role of Myc in mitochondrial biogenesis has not been directly established. We determined the effects of ectopic Myc expression or the loss of Myc on mitochondrial biogenesis. Induction of Myc in P493-6 cells resulted in increased oxygen consumption and mitochondrial mass and function. Conversely, compared to wild-type Myc fibroblasts, Myc null rat fibroblasts have diminished mitochondrial mass and decreased number of normal mitochondria. Reconstitution of Myc expression in Myc null fibroblasts partially restored mitochondrial mass and function and normal-appearing mitochondria. Concordantly, we also observed in primary hepatocytes that acute deletion of floxed murine Myc by Cre recombinase resulted in diminished mitochondrial mass in primary hepatocytes. Our microarray analysis of genes responsive to Myc in human P493-6 B lymphocytes supports a role for Myc in mitochondrial biogenesis, since genes involved in mitochondrial structure and function are overrepresented among the Myc-induced genes. In addition to the known direct binding of Myc to many genes involved in mitochondrial structure and function, we found that Myc binds the TFAM gene, which encodes a key transcriptional regulator and mitochondrial DNA replication factor, both in P493-6 lymphocytes with high ectopic MYC expression and in serum-stimulated primary human 2091 fibroblasts with induced endogenous MYC. These observations support a pivotal role for Myc in regulating mitochondrial biogenesis.

AB - Although several genes involved in mitochondrial function are direct Myc targets, the role of Myc in mitochondrial biogenesis has not been directly established. We determined the effects of ectopic Myc expression or the loss of Myc on mitochondrial biogenesis. Induction of Myc in P493-6 cells resulted in increased oxygen consumption and mitochondrial mass and function. Conversely, compared to wild-type Myc fibroblasts, Myc null rat fibroblasts have diminished mitochondrial mass and decreased number of normal mitochondria. Reconstitution of Myc expression in Myc null fibroblasts partially restored mitochondrial mass and function and normal-appearing mitochondria. Concordantly, we also observed in primary hepatocytes that acute deletion of floxed murine Myc by Cre recombinase resulted in diminished mitochondrial mass in primary hepatocytes. Our microarray analysis of genes responsive to Myc in human P493-6 B lymphocytes supports a role for Myc in mitochondrial biogenesis, since genes involved in mitochondrial structure and function are overrepresented among the Myc-induced genes. In addition to the known direct binding of Myc to many genes involved in mitochondrial structure and function, we found that Myc binds the TFAM gene, which encodes a key transcriptional regulator and mitochondrial DNA replication factor, both in P493-6 lymphocytes with high ectopic MYC expression and in serum-stimulated primary human 2091 fibroblasts with induced endogenous MYC. These observations support a pivotal role for Myc in regulating mitochondrial biogenesis.

UR - http://www.scopus.com/inward/record.url?scp=21744442902&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=21744442902&partnerID=8YFLogxK

U2 - 10.1128/MCB.25.14.6225-6234.2005

DO - 10.1128/MCB.25.14.6225-6234.2005

M3 - Article

VL - 25

SP - 6225

EP - 6234

JO - Molecular and Cellular Biology

JF - Molecular and Cellular Biology

SN - 0270-7306

IS - 14

ER -