Mitochondrial localization of MRN complex components in mammal cells

• Grant number: 18/04471-1
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: April 01, 2018
• End date: March 31, 2020
• Field of knowledge: Biological Sciences - Biochemistry - Molecular Biology
• Principal Investigator: Nadja Cristhina de Souza Pinto
• Grantee: Laís Yoshie Morikawa Muta
• Host Institution: Instituto de Química (IQ). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated research grant: 17/04372-0 - Mitochondrial DNA: mechanisms for genome integrity maintenance and impact on disease, AP.TEM

Abstract

Although the molecular mechanism that causes the formation and accumulation of deletions in the mtDNA is unknown, it has been proposed that somatic deletions result from incomplete or unresolved repair events, mainly during repair of double-strand breaks. Deletions in mtDNA are related to mitochondrial diseases like Kearns-Sayre syndrome and other complex diseases such as neurodegeneration and cancer. The molecular mechanisms of double strand break repair and the accumulation of lesions in the mtDNA are not as characterized as those that act on nuclear DNA. It is known that in the nucleus there are two pathways for double-strand breaks repair: non-homologous end joining and the homologous recombination pathway (HR). The HR pathway requires the MRN protein complex , formed by Mre11, Rad50, and Nbs1 subunits. Recently the presence of the Mre11 subunit has been observed in mouse kidney mitochondria, raising the possibility that the MRN complex may function in an analogous or similar manner as it does in the nucleus. To investigate such possibilities we will verify: (I) the presence of the Nbs1 subunit in HEK293T and HeLa cell mitochondria through immunofluorescence and western blot assays; and (II) whether Nbs1 mitochondrial localization and expression are altered by treatment with hydrogen peroxide, an agent that causes double-strand breaks in DNA.

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

FREIRE, T. S.; MORI, M. P.; MIRANDA, J. N. F. A.; MUTA, L. Y. M.; MACHADO, F. T.; MORENO, N. C.; SOUZA-PINTO, N. C.. Increased H2O2 levels and p53 stabilization lead to mitochondrial dysfunction in XPC-deficient cells. Carcinogenesis, v. 42, n. 11, p. 1380-1389, NOV 2021. (17/04372-0, 18/04471-1, 10/51906-1, 18/26555-2, 19/00480-9, 16/15407-7)