Role of mitochondrial dysfunction in the pathophysiology of DNA repair disorders

Author(s)

Mori, Mateus Prates ; de Souza-Pinto, Nadja Cristhina

• Document type: Journal article
• Source: Cell Biology International; v. 42, n. 6, p. 8-pg., 2018-06-01.

Abstract

DNA is constantly being damaged, either by endogenous or exogenous genotoxins. In that regard, DNA repair activities are essential for maintaining genomic stability and to life itself. Mutations in genes encoding DNA repair proteins cause severe human syndromes, but DNA repair defects have also been linked to several other diseases, notably to cancer and normal aging. Recently, new evidence has emerged indicating that some DNA repair diseases display mitochondrial and metabolic dysfunction through mechanisms that are yet being uncovered. These results suggest that mitochondria play an import role in the DNA damage response pathways and that damage accumulation may lead to mitochondrial dysfunction via metabolic imbalance and mitophagy impairment. Here we review the recent findings linking mitochondrial impairment and cell death to DNA damage accumulation in the context of DNA repair defects. In addition, the general involvement of DNA damage in cellular dysfunction suggests that these phenomena may be also involved in other human pathologies in which mitochondrial dysfunction and metabolic disruption play causative roles. (AU)

• 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
• 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