| Full text | |
| Author(s): |
Freire, T. S.
[1]
;
Mori, M. P.
[1]
;
Miranda, J. N. F. A.
[1]
;
Muta, L. Y. M.
[1]
;
Machado, F. T.
[1]
;
Moreno, N. C.
[1]
;
Souza-Pinto, N. C.
[1]
Total Authors: 7
|
| Affiliation: | [1] Univ Sao Paulo, Inst Quim, Dept Bioquim, BR-05508000 Sao Paulo, SP - Brazil
Total Affiliations: 1
|
| Document type: | Journal article |
| Source: | Carcinogenesis; v. 42, n. 11, p. 1380-1389, NOV 2021. |
| Web of Science Citations: | 0 |
| Abstract | |
XPC deficiency is associated with mitochondrial dysfunction, increased mitochondrial H(2)O(2 )production and sensitivity to the Complex III inhibitor antimycin A (AA), through a yet unclear mechanism. We found an imbalanced expression of several proteins that participate in important mitochondrial function and increased expression and phosphorylation of the tumor suppressor p53 in Xeroderma pigmentosum complementation group C (XP-C) (XPC-null) cells compared with an isogenic line corrected in locus with wild-type XPC (XPC-wt). Interestingly, inhibition of p53 nuclear import reversed the overexpression of mitochondrial proteins, whereas AA treatment increased p53 expression more strongly in the XP-C cells. However, inhibition of p53 substantially increased XP-C cellular sensitivity to AA treatment, suggesting that p53 is a critical factor mediating the cellular response to mitochondrial stress. On the other hand, treatment with the antioxidant N-acetylcysteine increased glutathione concentration and decreased basal H2O2 production, p53 levels and sensitivity to AA treatment in the XPC-null back to the levels found in XPC-wt cells. Thus, the results suggest a critical role for mitochondrially generated H2O2 in the regulation of p53 expression, which in turn modulates XP-C sensitivity to agents that cause mitochondrial stress. (AU) | |
| FAPESP's process: | 17/04372-0 - Mitochondrial DNA: mechanisms for genome integrity maintenance and impact on disease |
| Grantee: | Nadja Cristhina de Souza Pinto |
| Support Opportunities: | Research Projects - Thematic Grants |
| FAPESP's process: | 18/04471-1 - Mitochondrial localization of MRN complex components in mammal cells |
| Grantee: | Laís Yoshie Morikawa Muta |
| Support Opportunities: | Scholarships in Brazil - Scientific Initiation |
| FAPESP's process: | 10/51906-1 - Mitochondrial bioenergetics, ion transport, redox state and DNA metabolism |
| Grantee: | Alicia Juliana Kowaltowski |
| Support Opportunities: | Research Projects - Thematic Grants |
| FAPESP's process: | 18/26555-2 - Study of role of DNA polymerase eta in cellular responses and carcinogenesis induced by ultraviolet light A |
| Grantee: | Natália Cestari Moreno |
| Support Opportunities: | Scholarships in Brazil - Post-Doctoral |
| FAPESP's process: | 19/00480-9 - TT-3 Technical training scholarship, mitochondrial genetics Laboratory Dedication: 20 hours per week, 24 months |
| Grantee: | José Nivaldo Ferreira de Ataíde Miranda |
| Support Opportunities: | Scholarships in Brazil - Technical Training Program - Technical Training |
| FAPESP's process: | 16/15407-7 - Investigating the role of the TG mutation in XPC gene on expression of the transcriptional co-activator PGC-1a |
| Grantee: | Mateus Prates Mori |
| Support Opportunities: | Scholarships in Brazil - Post-Doctoral |