Mitochondrial control of nuclear apoptosis - PubMed (original) (raw)
Mitochondrial control of nuclear apoptosis
N Zamzami et al. J Exp Med. 1996.
Abstract
Anucleate cells can be induced to undergo programmed cell death (PCD), indicating the existence of a cytoplasmic PCD pathway that functions independently from the nucleus. Cytoplasmic structures including mitochondria have been shown to participate in the control of apoptotic nuclear disintegration. Before cells exhibit common signs of nuclear apoptosis (chromatin condensation and endonuclease-mediated DNA fragmentation), they undergo a reduction of the mitochondrial transmembrane potential (delta psi m) that may be due to the opening of mitochondrial permeability transition (PT) pores. Here, we present direct evidence indicating that mitochondrial PT constitutes a critical early event of the apoptotic process. In a cell-free system combining purified mitochondria and nuclei, mitochondria undergoing PT suffice to induce chromatin condensation and DNA fragmentation. Induction of PT by pharmacological agents augments the apoptosis-inducing potential of mitochondria. In contrast, prevention of PT by pharmacological agents impedes nuclear apoptosis, both in vitro and in vivo. Mitochondria from hepatocytes or lymphoid cells undergoing apoptosis, but not those from normal cells, induce disintegration of isolated Hela nuclei. A specific ligand of the mitochondrial adenine nucleotide translocator (ANT), bongkreik acid, inhibits PT and reduces apoptosis induction by mitochondria in a cell-free system. Moreover, it inhibits the induction of apoptosis in intact cells. Several pieces of evidence suggest that the proto-oncogene product Bcl-2 inhibits apoptosis by preventing mitochondrial PT. First, to inhibit nuclear apoptosis, Bcl-2 must be localized in mitochondrial but not nuclear membranes. Second, transfection-enforced hyperexpression of Bcl-2 directly abolishes the induction of mitochondrial PT in response to a protonophore, a pro-oxidant, as well as to the ANT ligand atractyloside, correlating with its apoptosis-inhibitory effect. In conclusion, mitochondrial PT appears to be a critical step of the apoptotic cascade.
Comment in
- Apoptosis: mitochondria resurrected?
Henkart PA, Grinstein S. Henkart PA, et al. J Exp Med. 1996 Apr 1;183(4):1293-5. doi: 10.1084/jem.183.4.1293. J Exp Med. 1996. PMID: 8666886 Free PMC article. No abstract available.
Similar articles
- Mitochondrial permeability transition triggers lymphocyte apoptosis.
Marchetti P, Hirsch T, Zamzami N, Castedo M, Decaudin D, Susin SA, Masse B, Kroemer G. Marchetti P, et al. J Immunol. 1996 Dec 1;157(11):4830-6. J Immunol. 1996. PMID: 8943385 - PK11195, a ligand of the mitochondrial benzodiazepine receptor, facilitates the induction of apoptosis and reverses Bcl-2-mediated cytoprotection.
Hirsch T, Decaudin D, Susin SA, Marchetti P, Larochette N, Resche-Rigon M, Kroemer G. Hirsch T, et al. Exp Cell Res. 1998 Jun 15;241(2):426-34. doi: 10.1006/excr.1998.4084. Exp Cell Res. 1998. PMID: 9637784 - Mitochondrial permeability transition is a central coordinating event of apoptosis.
Marchetti P, Castedo M, Susin SA, Zamzami N, Hirsch T, Macho A, Haeffner A, Hirsch F, Geuskens M, Kroemer G. Marchetti P, et al. J Exp Med. 1996 Sep 1;184(3):1155-60. doi: 10.1084/jem.184.3.1155. J Exp Med. 1996. PMID: 9064332 Free PMC article. - Role of the mitochondrial permeability transition pore in apoptosis.
Hirsch T, Marzo I, Kroemer G. Hirsch T, et al. Biosci Rep. 1997 Feb;17(1):67-76. doi: 10.1023/a:1027339418683. Biosci Rep. 1997. PMID: 9171922 Review. - Mitochondrial control of apoptosis: an overview.
Kroemer G. Kroemer G. Biochem Soc Symp. 1999;66:1-15. doi: 10.1042/bss0660001. Biochem Soc Symp. 1999. PMID: 10989652 Review.
Cited by
- Collective heterogeneity of mitochondrial potential in contact inhibition of proliferation.
Thurakkal B, Hari K, Marwaha R, Karki S, Jolly MK, Das T. Thurakkal B, et al. Biophys J. 2023 Oct 3;122(19):3909-3923. doi: 10.1016/j.bpj.2023.08.014. Epub 2023 Aug 19. Biophys J. 2023. PMID: 37598292 Free PMC article. - Chick Early Amniotic Fluid (ceAF) Deters Tumorigenesis via Cell Cycle Arrest and Apoptosis.
Ahmad M, Yu J, Cheng S, Khan ZA, Luo Y, Luo H. Ahmad M, et al. Biology (Basel). 2022 Oct 27;11(11):1577. doi: 10.3390/biology11111577. Biology (Basel). 2022. PMID: 36358278 Free PMC article. - Mitochondrial Damage of Lymphocytes in Patients with Acute Relapse of Schizophrenia: A Correlational Study with Efficacy and Clinical Symptoms.
Hu A, Li F, Guo L, Zhao X, Xiang X. Hu A, et al. Neuropsychiatr Dis Treat. 2022 Oct 27;18:2455-2466. doi: 10.2147/NDT.S380353. eCollection 2022. Neuropsychiatr Dis Treat. 2022. PMID: 36325435 Free PMC article. - ALYREF, a novel factor involved in breast carcinogenesis, acts through transcriptional and post-transcriptional mechanisms selectively regulating the short NEAT1 isoform.
Klec C, Knutsen E, Schwarzenbacher D, Jonas K, Pasculli B, Heitzer E, Rinner B, Krajina K, Prinz F, Gottschalk B, Ulz P, Deutsch A, Prokesch A, Jahn SW, Lellahi SM, Perander M, Barbano R, Graier WF, Parrella P, Calin GA, Pichler M. Klec C, et al. Cell Mol Life Sci. 2022 Jul 1;79(7):391. doi: 10.1007/s00018-022-04402-2. Cell Mol Life Sci. 2022. PMID: 35776213 Free PMC article. - Inhibition of B-cell lymphoma 2 family proteins alters optical redox ratio, mitochondrial polarization, and cell energetics independent of cell state.
Gillette AA, DeStefanis RA, Pritzl SL, Deming DA, Skala MC. Gillette AA, et al. J Biomed Opt. 2022 May;27(5):056505. doi: 10.1117/1.JBO.27.5.056505. J Biomed Opt. 2022. PMID: 35643815 Free PMC article.
References
- J Biol Chem. 1993 May 25;268(15):10920-6 - PubMed
- Ann N Y Acad Sci. 1993 Jun 23;685:330-5 - PubMed
- Cancer Res. 1993 Oct 1;53(19):4701-14 - PubMed
- Cell. 1993 Oct 22;75(2):241-51 - PubMed
- J Biol Chem. 1993 Oct 15;268(29):21939-45 - PubMed
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources