Mitochondrial DNA deletions sensitize cells to apoptosis at low heteroplasmy levels
- Institute of Neuropathology of the Otto-von-Guericke University, Leipziger Str. 44, 39120 Magdeburg (Germany)
- Institute of Forensic Medicine of the Otto-von-Guericke University, Leipziger Str. 44, 39120 Magdeburg (Germany)
- KeyNeurotek AG, Leipziger Str. 44, 39120 Magdeburg (Germany)
- Institute of Experimental Surgery of the Otto-von-Guericke University, Leipziger Str. 44, 39120 Magdeburg (Germany)
A heterogeneous group of multisystem disorders affecting various tissues and often including neuromuscular symptoms is caused by mutations of the mitochondrial genome, which codes 13 polypeptides of oxidative phosphorylation (OXPHOS) complexes and 22 tRNA genes needed for their translation. Since the link between OXPHOS dysfunction and clinical phenotype remains enigmatic in many diseases, a possible role of enhanced apoptosis is discussed besides bioenergetic crisis of affected cells. We analyzed the proapoptotic impact of the mitochondrial 5 kb common deletion (CD), affecting five tRNA genes, in transmitochondrial cybrid cell lines and found a slightly enhanced sensitivity to exogenous oxidative stress (H{sub 2}O{sub 2}) and a pronounced sensitization against death receptor stimulation (TRAIL) at a rather low CD heteroplasmy level of 22%. Mitochondrial deletions confer enhanced susceptibility against proapoptotic signals to proliferating cells, which might explain the elimination of deletions from hematopoietic stem cells.
- OSTI ID:
- 20710816
- Journal Information:
- Biochemical and Biophysical Research Communications, Vol. 332, Issue 1; Other Information: DOI: 10.1016/j.bbrc.2005.04.086; PII: S0006-291X(05)00869-7; Copyright (c) 2005 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA); ISSN 0006-291X
- Country of Publication:
- United States
- Language:
- English
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