Mitochondrial DNA oxidative damage and repair in aging and Alzheimer's disease

Renato X. Santos, Sonia C. Correia, Xiongwei Zhu, Mark A. Smith, Paula I. Moreira, Rudy J. Castellani, Akihiko Nunomura, George Perry

Research output: Contribution to journalArticlepeer-review

134 Citations (Scopus)


Significance: Mitochondria are fundamental to the life and proper functioning of cells. These organelles play a key role in energy production, in maintaining homeostatic levels of second messengers (e.g., reactive oxygen species and calcium), and in the coordination of apoptotic cell death. The role of mitochondria in aging and in pathophysiological processes is constantly being unraveled, and their involvement in neurodegenerative processes, such as Alzheimer's disease (AD), is very well known. Recent Advances: A considerable amount of evidence points to oxidative damage to mitochondrial DNA (mtDNA) as a determinant event that occurs during aging, which may cause or potentiate mitochondrial dysfunction favoring neurodegenerative events. Concomitantly to reactive oxygen species production, an inefficient mitochondrial base excision repair (BER) machinery has also been pointed to favor the accumulation of oxidized bases in mtDNA during aging and AD progression. Critical Issues: The accumulation of oxidized mtDNA bases during aging increases the risk of sporadic AD, an event that is much less relevant in the familial forms of the disease. This aspect is critical for the interpretation of data arising from tissue of AD patients and animal models of AD, as the major part of animal models rely on mutations in genes associated with familial forms of the disease. Future Directions: Further investigation is important to unveil the role of mtDNA and BER in aging brain and AD in order to design more effective preventive and therapeutic strategies. Antioxid. Redox Signal. 18, 2444–2457.
Original languageEnglish
Pages (from-to)2444–2457
Number of pages17
JournalAntioxidants & Redox Signaling
Issue number18
Early online date7 Dec 2012
Publication statusPublished - 3 Jun 2013
Externally publishedYes

Bibliographical note

Renato X. Santos is the recipient of a PhD fellowship from the Fundação para a Ciência e a Tecnologia (SFRH/BD/43972/2008). Work in the authors' laboratories is supported by Fundação para a Ciência e a Tecnologia and Fundo Europeu de Desenvolvimento Regional (PTDC/SAU-NEU/103325/2008 and PTDC/SAU-NMC/110990/2009). This project was also supported by a grant from the National Institute on Minority Health and Health Disparities (G12MD007591) from the National Institutes of Health.


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