Alterations of mitochondrial biogenesis in chronic lymphocytic leukemia cells with loss of p53

Marcia A. Ogasawara; Jinyun Liu; Helene Pelicano; Naima Hammoudi; Carlo M. Croce; Michael J. Keating; Peng Huang

doi:10.1016/j.mito.2016.09.001

Alterations of mitochondrial biogenesis in chronic lymphocytic leukemia cells with loss of p53

Marcia A. Ogasawara, Jinyun Liu, Helene Pelicano, Naima Hammoudi, Carlo M. Croce, Michael J. Keating, Peng Huang

Research output: Contribution to journal › Article › peer-review

9 Scopus citations

Abstract

Deletion of chromosome 17p with a loss of p53 is an unfavorable cytogenetic change in chronic lymphocytic leukemia (CLL) with poor clinical outcome. Since p53 affects mitochondrial function and integrity, we examined possible mitochondrial changes in CLL mice with TCL1-Tg/p53^−/− and TCL1-Tg/p53^+/+ genotypes and in primary leukemia cells from CLL patients with or without 17p-deletion. Although the expression of mitochondrial COX1, ND2, and ND6 decreased in p53^−/− CLL cells, there was an increase in mitochondrial biogenesis as evidenced by higher mitochondrial mass and mtDNA copy number associated with an elevated expression of TFAM and PGC-1α. Surprisingly, the overall mitochondrial respiratory activity and maximum reserved capacity increased in p53^−/− CLL cells. Our study suggests that leukemia cells lacking p53 seem able to maintain respiratory function by compensatory increase in mitochondrial biogenesis.

Original language	English (US)
Pages (from-to)	33-39
Number of pages	7
Journal	Mitochondrion
Volume	31
DOIs	https://doi.org/10.1016/j.mito.2016.09.001
State	Published - Nov 1 2016

Keywords

Chronic lymphocytic leukemia
Mitochondrial biogenesis
p53

ASJC Scopus subject areas

Molecular Medicine
Molecular Biology
Cell Biology

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10.1016/j.mito.2016.09.001

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title = "Alterations of mitochondrial biogenesis in chronic lymphocytic leukemia cells with loss of p53",

abstract = "Deletion of chromosome 17p with a loss of p53 is an unfavorable cytogenetic change in chronic lymphocytic leukemia (CLL) with poor clinical outcome. Since p53 affects mitochondrial function and integrity, we examined possible mitochondrial changes in CLL mice with TCL1-Tg/p53−/− and TCL1-Tg/p53+/+ genotypes and in primary leukemia cells from CLL patients with or without 17p-deletion. Although the expression of mitochondrial COX1, ND2, and ND6 decreased in p53−/− CLL cells, there was an increase in mitochondrial biogenesis as evidenced by higher mitochondrial mass and mtDNA copy number associated with an elevated expression of TFAM and PGC-1α. Surprisingly, the overall mitochondrial respiratory activity and maximum reserved capacity increased in p53−/− CLL cells. Our study suggests that leukemia cells lacking p53 seem able to maintain respiratory function by compensatory increase in mitochondrial biogenesis.",

keywords = "Chronic lymphocytic leukemia, Mitochondrial biogenesis, p53",

author = "Ogasawara, {Marcia A.} and Jinyun Liu and Helene Pelicano and Naima Hammoudi and Croce, {Carlo M.} and Keating, {Michael J.} and Peng Huang",

note = "Funding Information: The authors thank M.R. Nelson, B.A. Hayes and R. LaPushin for their assistance in handling CLL samples. This work was supported in part by grants CA085563 and CA172724 from the National Institutes of Health , a grant from the CLL Global Research Foundation, and the generous philanthropic contributions to the University of Texas MD Anderson CLL Moon Shot Program. Publisher Copyright: {\textcopyright} 2016 Elsevier B.V. and Mitochondria Research Society",

year = "2016",

month = nov,

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doi = "10.1016/j.mito.2016.09.001",

language = "English (US)",

volume = "31",

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AU - Ogasawara, Marcia A.

AU - Liu, Jinyun

AU - Pelicano, Helene

AU - Hammoudi, Naima

AU - Croce, Carlo M.

AU - Keating, Michael J.

AU - Huang, Peng

N1 - Funding Information: The authors thank M.R. Nelson, B.A. Hayes and R. LaPushin for their assistance in handling CLL samples. This work was supported in part by grants CA085563 and CA172724 from the National Institutes of Health , a grant from the CLL Global Research Foundation, and the generous philanthropic contributions to the University of Texas MD Anderson CLL Moon Shot Program. Publisher Copyright: © 2016 Elsevier B.V. and Mitochondria Research Society

PY - 2016/11/1

Y1 - 2016/11/1

N2 - Deletion of chromosome 17p with a loss of p53 is an unfavorable cytogenetic change in chronic lymphocytic leukemia (CLL) with poor clinical outcome. Since p53 affects mitochondrial function and integrity, we examined possible mitochondrial changes in CLL mice with TCL1-Tg/p53−/− and TCL1-Tg/p53+/+ genotypes and in primary leukemia cells from CLL patients with or without 17p-deletion. Although the expression of mitochondrial COX1, ND2, and ND6 decreased in p53−/− CLL cells, there was an increase in mitochondrial biogenesis as evidenced by higher mitochondrial mass and mtDNA copy number associated with an elevated expression of TFAM and PGC-1α. Surprisingly, the overall mitochondrial respiratory activity and maximum reserved capacity increased in p53−/− CLL cells. Our study suggests that leukemia cells lacking p53 seem able to maintain respiratory function by compensatory increase in mitochondrial biogenesis.

AB - Deletion of chromosome 17p with a loss of p53 is an unfavorable cytogenetic change in chronic lymphocytic leukemia (CLL) with poor clinical outcome. Since p53 affects mitochondrial function and integrity, we examined possible mitochondrial changes in CLL mice with TCL1-Tg/p53−/− and TCL1-Tg/p53+/+ genotypes and in primary leukemia cells from CLL patients with or without 17p-deletion. Although the expression of mitochondrial COX1, ND2, and ND6 decreased in p53−/− CLL cells, there was an increase in mitochondrial biogenesis as evidenced by higher mitochondrial mass and mtDNA copy number associated with an elevated expression of TFAM and PGC-1α. Surprisingly, the overall mitochondrial respiratory activity and maximum reserved capacity increased in p53−/− CLL cells. Our study suggests that leukemia cells lacking p53 seem able to maintain respiratory function by compensatory increase in mitochondrial biogenesis.

KW - Chronic lymphocytic leukemia

KW - Mitochondrial biogenesis

KW - p53

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Alterations of mitochondrial biogenesis in chronic lymphocytic leukemia cells with loss of p53

Abstract

Keywords

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