Mutagenesis, tumorigenicity, and apoptosis: are the mitochondria involved?

Early studies have shown mitochondrially-mediated oxidative phosphorylation is diminished in cancer cells, with glycolysis being the main source of energy production. More recent provocative reports have indicated that the mitochondria may be involved in a host of different aspects of tumorigenesis, including mutagenesis, maintenance of the malignant phenotype, and control of apoptosis. These studies have broadened the possible roles mitochondria may play in malignancy. Further studies to define the importance of mitochondria should revolve around the functional assessment of these changes in vitro and in vivo, and will be interesting for determining their significance in human cancer.

[1]  R. Sager,et al.  Tumorigenicity and its suppression in cybrids of mouse and Chinese hamster cell lines. , 1978, Proceedings of the National Academy of Sciences of the United States of America.

[2]  D. Newmeyer,et al.  Cell-free apoptosis in Xenopus egg extracts: Inhibition by Bcl-2 and requirement for an organelle fraction enriched in mitochondria , 1994, Cell.

[3]  D. Green,et al.  Cell‐free reconstitution of Fas‐, UV radiation‐ and ceramide‐induced apoptosis. , 1995, The EMBO journal.

[4]  M. Raff,et al.  Programmed cell death and Bcl‐2 protection in the absence of a nucleus. , 1994, The EMBO journal.

[5]  S. Tourmente,et al.  Expression of six mitochondrial genes during Drosophila oogenesis: analysis by in situ hybridization. , 1990, Cell differentiation and development : the official journal of the International Society of Developmental Biologists.

[6]  K. Schulze-Osthoff,et al.  Cell nucleus and DNA fragmentation are not required for apoptosis , 1994, The Journal of cell biology.

[7]  V. Egilsson,et al.  Mitochondria, cell surface, and carcinogenesis. , 1983, International review of cytology. Supplement.

[8]  C. Guguen-Guillouzo,et al.  Increased level of the mitochondrial ND5 transcript in chemically induced rat hepatomas. , 1989, Experimental cell research.

[9]  I. Evans,et al.  Mitochondria and the yeast cell surface: implications for carcinogenesis , 1982 .

[10]  C. Smith,et al.  Complex mitochondrial DNA. , 1975, International review of experimental pathology.

[11]  F. Babai,et al.  Tumor-forming ability in athymic nude mice of human cell lines devoid of mitochondrial DNA. , 1994, Cancer research.

[12]  R. Newbold,et al.  Induction of immortality is an early event in malignant transformation of mammalian cells by carcinogens , 1982, Nature.

[13]  P. Thorsness,et al.  Escape of DNA from mitochondria to the nucleus in Saccharomyces cerevisiae , 1990, Nature.

[14]  R. Schekman,et al.  Regulated import and degradation of a cytosolic protein in the yeast vacuole , 1991, Nature.

[15]  John Calvin Reed,et al.  Identification of a p53-dependent negative response element in the bcl-2 gene. , 1994, Cancer research.

[16]  A. Gianni,et al.  Restriction enzyme analysis of human leukemic mitochondrial DNA. , 1980, Leukemia research.

[17]  G. Kovacs,et al.  Alteration of mitochondrial DNA in human oncocytomas , 1989, Genes, chromosomes & cancer.

[18]  G. Kroemer,et al.  Inhibitors of permeability transition interfere with the disruption of the mitochondrial transmembrane potential during apoptosis , 1996, FEBS letters.

[19]  N. Howell,et al.  Genetic analysis of tumorigenesis. VIII. Suppression of SV40 transformation in cell hybrids and cytoplasmic transferants. , 1981, Cytogenetics and cell genetics.

[20]  E. White,et al.  Bcl-2 blocks p53-dependent apoptosis , 1994, Molecular and cellular biology.

[21]  S. Lowe,et al.  p53 modulation of anchorage independent growth and experimental metastasis. , 1996, Oncogene.

[22]  G. Kroemer,et al.  Mitochondrial perturbations define lymphocytes undergoing apoptotic depletion in vivo , 1995, European journal of immunology.

[23]  D. Wallace,et al.  Mitochondrial genetics: principles and practice. , 1992, American journal of human genetics.

[24]  Andy J. Minn,et al.  Bcl-xL forms an ion channel in synthetic lipid membranes , 1997, Nature.

[25]  H Harris,et al.  The analysis of malignancy by cell fusion. I. Hybrids between tumour cells and L cell derivatives. , 1971, Journal of cell science.

[26]  G. Kroemer,et al.  Reduction in mitochondrial potential constitutes an early irreversible step of programmed lymphocyte death in vivo , 1995, The Journal of experimental medicine.

[27]  K. Tewari,et al.  Biochemical properties of neoplastic cell mitochondria. , 1974, Journal of the National Cancer Institute.

[28]  A. Harding,et al.  Deletions of muscle mitochondrial DNA in patients with mitochondrial myopathies , 1988, Nature.

[29]  J. Palmer,et al.  RNA-mediated transfer of the gene coxII from the mitochondrion to the nucleus during flowering plant evolution , 1991, Cell.

[30]  J. Shay,et al.  New evidence for the insertion of mitochondrial DNA into the human genome: significance for cancer and aging. , 1992, Mutation research.

[31]  R. Morais,et al.  Ethidium bromide-induced loss of mitochondrial DNA from primary chicken embryo fibroblasts , 1985, Molecular and cellular biology.

[32]  P. Ossorio,et al.  Mitochondrial-like DNA sequences flanked by direct and inverted repeats in the nuclear genome of Toxoplasma gondii. , 1991, Journal of molecular biology.

[33]  J. Slightom,et al.  Mitochondrial D-loop sequences are integrated in the rat nuclear genome. , 1991, Journal of molecular biology.

[34]  R. Morais,et al.  On suppression of tumorigenicity in hybrid and cybrid mouse cells , 1981, Somatic Cell Genetics.

[35]  D. Burk.  A COLLOQUIAL CONSIDERATION OF THE PASTEUR AND NEO-PASTEUR EFFECTS , 1939 .

[36]  P. Petit,et al.  Alterations in mitochondrial structure and function are early events of dexamethasone-induced thymocyte apoptosis , 1995, The Journal of cell biology.

[37]  R. Morais,et al.  Mitochondrial DNA modulation of the anchorage-independent phenotype of transformed avian cells. , 1990, Cancer research.

[38]  M. Taira,et al.  Tumor-associated mutations of rat mitochondrial transfer RNA genes. , 1983, Nucleic acids research.

[39]  H. Harris,et al.  The analysis of malignancy by cell fusion. VIII. Evidence for the intervention of an extra-chromosomal element. , 1977, Journal of cell science.

[40]  H. Sakamaki,et al.  Giant mitochondria in acute lymphocytic leukemia. , 1987, Experimental and molecular pathology (Print).

[41]  M. King,et al.  Human cells lacking mtDNA: repopulation with exogenous mitochondria by complementation. , 1989, Science.

[42]  L. Baggetto.  Role of mitochondria in carcinogenesis. , 1992, European journal of cancer.

[43]  A. Kitzis,et al.  DNA sequences homologous to mitochondrial genes in nuclei from normal rat tissues and from rat hepatoma cells. , 1989, Biochemical and biophysical research communications.

[44]  J. Shay,et al.  HeLaTG cells have mitochondrial DNA inserted into the c-myc oncogene. , 1991, Oncogene.

[45]  M. M. Nass.  Differential effects of ethidium bromide on mitochondrial and nuclear DNA synthesis in vivo in cultured mammalian cells. , 1972, Experimental cell research.

[46]  O. Warburg.  On respiratory impairment in cancer cells. , 1956, Science.

[47]  B. Lloveras,et al.  Bcl‐2 expression is associated with lymph node metastasis in human ductal breast carcinoma , 1995, International journal of cancer.

[48]  G. Kroemer,et al.  Bcl-2 and Bcl-XL antagonize the mitochondrial dysfunction preceding nuclear apoptosis induced by chemotherapeutic agents. , 1997, Cancer research.

[49]  L. Augenlicht,et al.  Short-chain fatty acid-initiated cell cycle arrest and apoptosis of colonic epithelial cells is linked to mitochondrial function. , 1997, Cell growth & differentiation : the molecular biology journal of the American Association for Cancer Research.

[50]  G. Gellissen,et al.  Gene Transfer a , 1987, Annals of the New York Academy of Sciences.

[51]  Y. Nimura,et al.  Significant existence of deleted mitochondrial DNA in cirrhotic liver surrounding hepatic tumor. , 1992, Biochemical and biophysical research communications.

[52]  Guido Kroemer,et al.  The biochemistry of programmed cell death , 1995, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[53]  T. Kristensen,et al.  The presence of intact mitochondrial DNA in HeLa cell nuclei. , 1986, Nucleic Acids Research.

[54]  B. Liang,et al.  Evidence for association of mitochondrial DNA sequence amplification and nuclear localization in human low-grade gliomas. , 1996, Mutation research.

[55]  O. Warburg.  [Origin of cancer cells]. , 1956, Oncologia.

[56]  Ronald A. Butow,et al.  Rearranged mitochondrial genes in the yeast nuclear genome , 1983, Nature.

[57]  S. Tsuboi,et al.  Ultrastructural analysis of the autophagic process in yeast: detection of autophagosomes and their characterization , 1994, The Journal of cell biology.

[58]  K. H. White,et al.  Mitochondrial morphological and functional defects in yeast caused by yme1 are suppressed by mutation of a 26S protease subunit homologue. , 1994, Molecular biology of the cell.

[59]  S. Burgess,et al.  MMM1 encodes a mitochondrial outer membrane protein essential for establishing and maintaining the structure of yeast mitochondria , 1994, The Journal of cell biology.

[60]  S. Weinhouse.  Oxidative metabolism of neoplastic tissues. , 1955, Advances in cancer research.

[61]  P. Thorsness,et al.  Nuclear mutations in Saccharomyces cerevisiae that affect the escape of DNA from mitochondria to the nucleus. , 1993, Genetics.

[62]  G. Kroemer,et al.  Apoptosis-associated derangement of mitochondrial function in cells lacking mitochondrial DNA. , 1996, Cancer research.

[63]  Dean P. Jones,et al.  Prevention of Apoptosis by Bcl-2: Release of Cytochrome c from Mitochondria Blocked , 1997, Science.

[64]  D. A. Clayton,et al.  Circular Dimer and Catenate Forms of Mitochondrial DNA in Human Leukaemic Leucocytes , 1967, Nature.

[65]  G. D. Clark-Walker,et al.  Abnormal Mitochondrial DNA in Acute Leukaemia and Lymphoma , 1979, British journal of haematology.

[66]  D. Green,et al.  The Release of Cytochrome c from Mitochondria: A Primary Site for Bcl-2 Regulation of Apoptosis , 1997, Science.

[67]  R. Morais,et al.  On the tumorigenicity of mitochondrial DNA-depleted avian cells. , 1991, Cancer letters.

[68]  H. Morris,et al.  Ultrastructure of Morris renal tumors. , 1973, Journal of the National Cancer Institute.

[69]  C. Franceschi,et al.  Protective effect of N-acetylcysteine in tumor necrosis factor-alpha-induced apoptosis in U937 cells: the role of mitochondria. , 1995, Experimental cell research.